Low glycaemic index or low glycaemic load diets for people with overweight or obesity

Abstract

Background

The prevalence of obesity is increasing worldwide, yet nutritional management remains contentious. It has been suggested that low glycaemic index (GI) or low glycaemic load (GL) diets may stimulate greater weight loss than higher GI/GL diets or other weight reduction diets. The previous version of this review, published in 2007, found mainly short‐term intervention studies. Since then, randomised controlled trials (RCTs) with longer‐term follow‐up have become available, warranting an update of this review.

Objectives

To assess the effects of low glycaemic index or low glycaemic load diets on weight loss in people with overweight or obesity.

Search methods

We searched CENTRAL, MEDLINE, one other database, and two clinical trials registers from their inception to 25 May 2022. We did not apply any language restrictions.

Selection criteria

We included RCTs with a minimum duration of eight weeks comparing low GI/GL diets to higher GI/GL diets or any other diets in people with overweight or obesity.

Data collection and analysis

We used standard Cochrane methods. We conducted two main comparisons: low GI/GL diets versus higher GI/GL diets and low GI/GL diets versus any other diet. Our main outcomes included change in body weight and body mass index, adverse events, health‐related quality of life, and mortality. We used GRADE to assess the certainty of the evidence for each outcome.

Main results

In this updated review, we included 10 studies (1210 participants); nine were newly‐identified studies. We included only one study from the previous version of this review, following a revision of inclusion criteria. We listed five studies as 'awaiting classification' and one study as 'ongoing'. Of the 10 included studies, seven compared low GI/GL diets (233 participants) with higher GI/GL diets (222 participants) and three studies compared low GI/GL diets (379 participants) with any other diet (376 participants). One study included children (50 participants); one study included adults aged over 65 years (24 participants); the remaining studies included adults (1136 participants). The duration of the interventions varied from eight weeks to 18 months. All trials had an unclear or high risk of bias across several domains. 

Low GI/GL diets versus higher GI/GL diets

Low GI/GL diets probably result in little to no difference in change in body weight compared to higher GI/GL diets (mean difference (MD) ‐0.82 kg, 95% confidence interval (CI) ‐1.92 to 0.28; I² = 52%; 7 studies, 403 participants; moderate‐certainty evidence). Evidence from four studies reporting change in body mass index (BMI) indicated low GI/GL diets may result in little to no difference in change in BMI compared to higher GI/GL diets (MD ‐0.45 kg/m², 95% CI ‐1.02 to 0.12; I² = 22%; 186 participants; low‐certainty evidence)at the end of the study periods. One study assessing participants' mood indicated that low GI/GL diets may improve mood compared to higher GI/GL diets, but the evidence is very uncertain (MD ‐3.5, 95% CI ‐9.33 to 2.33; 42 participants; very low‐certainty evidence). Two studies assessing adverse events did not report any adverse events; we judged this outcome to have very low‐certainty evidence. No studies reported on all‐cause mortality.   

For the secondary outcomes, low GI/GL diets may result in little to no difference in fat mass compared to higher GI/GL diets (MD ‐0.86 kg, 95% CI ‐1.52 to ‐0.20; I² = 6%; 6 studies, 295 participants; low certainty‐evidence). Similarly, low GI/GL diets may result in little to no difference in fasting blood glucose level compared to higher GI/GL diets (MD 0.12 mmol/L, 95% CI 0.03 to 0.21; I² = 0%; 6 studies, 344 participants; low‐certainty evidence). 

Low GI/GL diets versus any other diet

Low GI/GL diets probably result in little to no difference in change in body weight compared to other diets (MD ‐1.24 kg, 95% CI ‐2.82 to 0.34; I² = 70%; 3 studies, 723 participants; moderate‐certainty evidence). The evidence suggests that low GI/GL diets probably result in little to no difference in change in BMI compared to other diets (MD ‐0.30 kg in favour of low GI/GL diets, 95% CI ‐0.59 to ‐0.01; I² = 0%; 2 studies, 650 participants; moderate‐certainty evidence). Two adverse events were reported in one study: one was not related to the intervention, and the other, an eating disorder, may have been related to the intervention. Another study reported 11 adverse events, including hypoglycaemia following an oral glucose tolerance test. The same study reported seven serious adverse events, including kidney stones and diverticulitis. We judged this outcome to have low‐certainty evidence. No studies reported on health‐related quality of life or all‐cause mortality.

For the secondary outcomes, none of the studies reported on fat mass. Low GI/GL diets probably do not reduce fasting blood glucose level compared to other diets (MD 0.03 mmol/L, 95% CI ‐0.05 to 0.12; I² = 0%; 3 studies, 732 participants; moderate‐certainty evidence). 

Authors' conclusions

The current evidence indicates there may be little to no difference for all main outcomes between low GI/GL diets versus higher GI/GL diets or any other diet. There is insufficient information to draw firm conclusions about the effect of low GI/GL diets on people with overweight or obesity. Most studies had a small sample size, with only a few participants in each comparison group. We rated the certainty of the evidence as moderate to very low. More well‐designed and adequately‐powered studies are needed. They should follow a standardised intervention protocol, adopt objective outcome measurement since blinding may be difficult to achieve, and make efforts to minimise loss to follow‐up. Furthermore, studies in people from a wide range of ethnicities and with a wide range of dietary habits, as well as studies in low‐ and middle‐income countries, are needed. 

Plain language summary

Do low glycaemic index or low glycaemic load diets help people with overweight or obesity to lose weight?

Key messages

‐ Low glycaemic index and low glycaemic load diets probably result in little to no difference in weight, compared to higher glycaemic index or load diets or any other diets.

‐ We are very uncertain of the effects of these diets on people's quality of life, side effects, and death.

What is a low glycaemic index or a low glycaemic load diet?

Low glycaemic index and low glycaemic load diets consist of foods that produce a milder or delayed peak in blood sugar. This may cause the body to produce less insulin, which could lead to weight loss.

What did we want to find out?

We wanted to evaluate the effects of following these diets in people with overweight or obesity. We checked the effects on weight, quality of life, side effects, and death. 

What did we do?
We looked for studies that compared the effects of these diets in adults with overweight or obesity with other diets, including high glycaemic index or high glycaemic load diets (diets that would produce a higher peak in blood sugar). The studies had to have a follow‐up of at least 8 weeks.

What did we find?

We included 10 studies with 1210 people (4.1% of participants were children and 1.9% were adults over 65 years old). Half of the studies were carried out in the USA, and there was one study each in Australia, Iran, Mexico, New Zealand, and Spain. 

Main results

Low glycaemic index or glycaemic load diets compared to higher glycaemic index or glycaemic load diets

Low glycaemic index or glycaemic load diets probably result in little to no difference in change in body weight. Results indicated that a low glycaemic index or glycaemic load diet may improve mood, but the actual effect is likely substantially different from the estimate of the effect. None of the participants experienced unwanted or harmful effects. None of the studies reported on deaths.

Low glycaemic index or glycaemic load diets compared to any other diets

Low glycaemic index or glycaemic load diets likely result in little to no difference in body weight change compared to other diets. Participants in the studies reported experiencing unwanted effects, including eating disorders, kidney stones, and diverticulitis (infection or inflammation of pouches that can form in your intestines; the pouches are called diverticula). These effects may or may not have been caused by the intervention. None of the studies for this comparison reported on participants' quality of life or deaths.

What are the limitations of the evidence?

We were most certain about the findings related to weight, but there were greater uncertainties for other results. Not all studies reported what happened regarding participants' quality of life and deaths, and most of the studies were very small. Also, participants in many studies knew which diets they received, which might have influenced how they lived during the study and how the study outcomes were measured. 

How up to date is this review?

The evidence is up to date to May 2022. 

Summary of findings

Summary of findings 1. Low glycaemic index (GI) or glycaemic load (GL) diets compared to higher GI or GL diets for people with obesity or overweight.

Low GI or GL diets compared to higher GI or GL diets for people with overweight or obesity
Patient or population: people with overweight or obesity Setting: community setting/free‐living individuals; USA, Australia, Mexico, New Zealand, and Spain Intervention: low GI or GL diets Comparison: higher GI or GL diets
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with higher GI or GL diets	Risk with Low GI or GL diets
Body weight (kg) Follow‐up: range 8 weeks to 18 months	The mean change in body weight (kg) ranged from ‐9 to ‐2.4 kg	0.82 kg lower (1.92 lower to 0.28 higher)	‐	403 (7 RCTs)	⊕⊕⊕⊝ Moderatea	‐
Body mass index (BMI) (kg/m2) Follow‐up: range 8 weeks to 18 months	The mean change in BMI (kg/m2) ranged from ‐3.2 to ‐1 kg/m2	0.45 kg/m2 lower (1.02 lower to 0.12 higher)	‐	186 (4 RCTs)	⊕⊕⊝⊝ Lowb	‐
Adverse events (n/N)	Study population		‐	106 (2 RCTs)	⊕⊝⊝⊝ Very lowc	Two studies assessing adverse events did not report any adverse event (Armendariz‐Anguiano 2011; Das 2007)
	See comment	See comment
Health‐related quality of life Scale range: 0 to 4 (higher value means greater disturbed mood), assessed with Profile of Mood States (POMS) questionnaire Follow‐up: 3 months	The mean health‐related quality of life was 0.4	3.5 lower (9.33 lower to 2.33 higher)	‐	42 (1 RCT)	⊕⊝⊝⊝ Very lowd	‐
All‐cause mortality	‐	‐	‐	‐	‐	No trial reported on all‐cause mortality
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). BMI: body mass index; CI: confidence interval; RCT: randomised controlled trial
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded one level for risk of bias: the blinding of participants and personnel for nutritional intervention is difficult, if not impossible in most cases, thus indicating unclear risk of bias. 
^bDowngraded one level for risk of bias: the blinding of participants and personnel for nutritional intervention is difficult, if not impossible in most cases, thus indicating unclear risk of bias. Downgraded one level for imprecision: small number of participants.
^cDowngraded one level for risk of bias: the blinding of participants and personnel for nutritional intervention is difficult, if not impossible in most cases, thus indicating unclear risk of bias. Downgraded two levels for imprecision: small number of participants and no events were reported. 
^dDowngraded one level for risk of bias: the blinding of participants and personnel for nutritional intervention is difficult, if not impossible in most cases, thus indicating unclear risk of bias. Outcome is self‐reported. Downgraded two levels for imprecision:  a single study was included with a  wide confidence interval.

Summary of findings 2. Low glycaemic index (GI) or low glycaemic load (GL) diets compared to any other diet for people with obesity or overweight.

Low GI or GL diets compared to any other diet for people with obesity or overweight
Patient or population: people with obesity or overweight Setting: community setting/free‐living individuals; USA and Iran Intervention: low GI or GL diets Comparison: any other diet (low‐fat diets and healthy nutritional recommendations‐based diet)
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
	Risk with any other diet	Risk with Low GI or GL diets
Body weight (kg) Follow‐up: range 10 weeks to 18 months	The mean change in body weight (kg) ranged from ‐5.29 to ‐1.2 kg	1.24 kg lower (‐2.82 lower to 0.34 higher)	‐	723 (3 RCTs)	⊕⊕⊕⊝ Moderatea	Comparator diets were low‐fat diets and a healthy nutritional recommendations‐based diet
Body mass index (BMI) (kg/m2) Follow‐up: range 10 weeks to 18 months	The mean change in BMI (kg/m2) ranged from ‐1.75 to ‐1.07 kg/m2	0.3 kg/m2 lower (0.59 lower to 0.01 higher)	‐	650 (2 RCTs)	⊕⊕⊕⊝ Moderatea	Comparator diets were low‐fat diets and a healthy nutritional recommendations‐based diet
Adverse events (n/N)	‐		‐	682 (2 RCTs)	⊕⊝⊝⊝ Lowa,b	Comparator diets were low‐fat diets. Two studies reporting on adverse events did not report events separately for intervention and comparator groups (Ebbeling 2007; Gardner 2018); meta‐analysis was not possible.
Health‐related quality of life	‐	‐	‐	‐	‐	No trials reported on health‐related quality of life
All‐cause mortality	‐	‐	‐	‐	‐	No trials reported on all‐cause mortality
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RCT: randomised controlled trial
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

^aDowngraded one level for risk of bias: the blinding of participants and personnel for nutritional intervention is difficult, if not impossible in most cases, thus indicating unclear risk of bias. 
^bDowngraded one level for imprecision: the adverse events were relatively low in number (20 in total); adverse events were not reported separately according to allocation; and some were considered unrelated to the assigned interventions, while others were considered to have an unclear association with the assigned interventions. 

Background

Description of the condition

Obesity is defined as an increase in body weight beyond the limitations of skeletal and physical requirement, as the result of an excessive accumulation of fat in the body (Sikaris 2004). It is widely acknowledged not only as a risk factor for non‐communicable diseases, but also as a complex condition linked to and caused by many metabolic and psychological drivers (Bray 2017). Obesity is commonly measured by the body mass index (BMI), calculated as body weight in kilograms divided by height in metres squared (kg/m²). According to the World Health Organization (WHO), in 2016, around 40%, or 2000 million, of the world's adult population were overweight (BMI ≥ 25 kg/m²), and 13%, or 650 million, were considered obese (BMI ≥ 30 kg/m²) (WHO 2018). 

Obesity affects most aspects of life, including causing physical and mental health morbidities, limiting physical functions, reducing overall productivity, and affecting health‐related quality of life (Aune 2016; Bell 2015; Bhaskaran 2014; Kasen 2008; Luppino 2010; Mongraw‐Chaffin 2015; Roberts 2003). Obesity is associated with a higher risk of non‐communicable diseases, such as hypertension, type 2 diabetes, and cardiovascular disease (Bradshaw 2019; Magkos 2016; Nyberg 2018), which are important causes of death globally. 

Obesity is a leading risk factor for type 2 diabetes, affecting children and adults worldwide (Leitner  2017). The International Diabetes Federation reported that one in 10, or 537 million, adults aged 20 to 79 years old are living with diabetes worldwide (International Diabetes Federation 2021). The increase in type 2 diabetes in people with obesity may relate to the relative insulin resistance obesity confers. The common occurrence of obesity and diabetes has led to the term diabesity (Kalra 2013; Pardo 2019). Poorly‐controlled diabetes may be complicated by retinopathy, nephropathy, neuropathy, and vascular diseases. Good glycaemic control is crucial to reducing the complications of diseases, improving the quality and duration of life, and minimising the need for expensive health care.

Although several factors – including genetic, behavioural, and metabolic – can play a role in affecting body weight, the fundamental cause of obesity and overweight is an energy imbalance between calories consumed and calories used. This is due to a combination of increased intake of energy‐dense foods and a decrease in physical activity. These population‐level changes are a result of a complex web of environmental and societal changes across many sectors, including health, agriculture, transport, urban planning, environment, food processing, distribution, marketing, and education (WHO 2020).

A systematic review of international, evidence‐based guidelines recommends that people with overweight or obesity should lose 5% to 10% of body weight – in line with recommendations by the Centres for Disease Control and Prevention (CDC 2020) – to lower the risk of non‐communicable diseases associated with obesity and to improve overall health (Semlitsch 2019). For people with overweight or obesity, losing 15% of body weight is associated with even more favourable health outcomes (Knell 2018). Body weight reduction can be achieved through dietary modification. In general, a daily restriction of energy intake can lead to weight reduction (Gargallo 2012; Semlitsch 2019). However, with the emergence of a multitude of diets with varied outcomes on body weight, it is unclear which diets are the most effective and safe for particular populations (Smethers 2018).

Description of the intervention

Nutritional management in people with overweight or obesity varies greatly, due to a lack of consensus amongst clinicians on the best approach. This, in part, reflects the lack of good‐quality trials. Authors of systematic reviews of low‐carbohydrate diets found there was insufficient evidence to make recommendations for or against their use (Bravata 2003; Hamdy 2018). Hamdy and colleagues suggest further research should be conducted to determine the best dietary composition for achieving the maximum benefit for weight management, glycaemic control, and cardiovascular risk factors (Hamdy 2018).

Traditionally, carbohydrates were characterised as 'simple' or 'complex', based on the hypothesis that one or two glucose molecules in simple sugars would cause a larger increase in blood glucose compared to long chains of glucose molecules in complex carbohydrates. However, research has shown that, much like simple carbohydrates, complex carbohydrates (such as rice, potatoes, and bread) cause a significant increase in blood glucose (Atkinson 2008). The concepts of glycaemic index (GI) and glycaemic load (GL) have been established in order to rank foods according to their effect on blood glucose. 

Jenkins and colleagues first introduced the term 'glycaemic index' (Jenkins 1981). This concept extends a hypothesis on dietary fibre which states that foods which are absorbed slowly may be metabolically beneficial for diabetes and may reduce the risks of coronary heart disease (Burkitt 1977; Jenkins 2002). The glycaemic index is a relative ranking of how carbohydrates in foods affect postprandial blood glucose levels. Low GI foods, such as lentils, provide a slower and more consistent source of glucose to the bloodstream, thereby stimulating less insulin release than high GI foods, such as white bread (Jenkins 1981). Glycaemic index values are determined by calculating the incremental area under the blood glucose response curve (iAUC) of 50 g of available carbohydrate from a test food divided by the iAUC of the same amount of carbohydrate from a standard food (50 g of glucose solution) consumed by the same individual under standard conditions (FAO/WHO 1997). Thus, the GI concept focuses on the difference in blood glucose response after the ingestion of the same amount of carbohydrates from different foods. It is thought that these differences may have implications for health, performance, and well‐being, and could be utilised as a strategy to prevent and manage chronic diseases, such as cardiovascular diseases and diabetes (Jenkins 1995). 

The GI classifications of foods are as follows: low (≤ 55), medium (56 to 69) or high (≥ 70), where glucose is set as a reference with a value of 100. The daily total glycaemic index of a low GI diet should be kept at 45 or below (GIF 2017a).

In common practice, the portion size of food differs and so does the amount of carbohydrates consumed from a single portion of varied foods. The concept of glycaemic load (GL) was introduced to address this issue. Glycaemic load is determined as the total amount of carbohydrate (in grams) in a food multiplied by the food’s GI value divided by 100 (GL = g carbohydrate x GI/100) (Vrolix 2010). A food or meal with a GL value of 10 or less is considered as low, 11 to 19 as medium, and 20 or more as high. The total daily glycaemic load of a low GL diet should be kept at 100 or below (GIF 2017b). The introduction of the GL concept allows a comparison to be made between the probable glycaemic effect of realistic portions of foods that contain different amounts of carbohydrates (Salmeron 1997). For example, watermelon has been claimed to have a considerably high GI value. However, the amount of carbohydrates in a single serving is small, therefore giving it a low GL value. Thus, considering the quantity of carbohydrates and the GI value of a food is more reflective of the postprandial glycaemic response of a specific portion.

The GI of foods is greatly influenced by a variety of factors that can be classified into two groups: (1) factors related to the food's nutrient content; and (2) factors related to the preparation or cooking methods involved. The consumption of carbohydrate‐dense foods combined with greater amounts of dietary fibre, protein, fats, or organic acids lowers the postprandial glycaemic response (Bell 2015; Hlebowicz 2007; Weickert 2018). However, this effect may not be similar for all types of foods. Different sources of proteins and fats have different effects on the glycaemic response, despite being consumed with the same type and quantity of carbohydrates (Bell 2015; Mueller 2012; Quek 2016). For example, the consumption of rice‐based meals with soybean curd significantly reduced the postprandial glucose response compared to rice plus other protein sources, such as fish, egg, and chicken.

Several randomised controlled studies suggest that consumption of low GI and GL diets may reduce body weight, increase insulin sensitivity, and reduce cardiovascular risk factors (Armendariz 2011; Pereira 2015; Philippou 2009). The postulated adverse effects of low GI and GL diets include gastrointestinal side effects (e.g. flatulence and diarrhoea) due to higher fibre consumption as part of a lower GI diet (Hartley 2016). 

How the intervention might work

Low GI foods may increase insulin sensitivity by minimising fluctuations in blood glucose levels and reducing the secretion of insulin over the day (Kiens 1996). There is some evidence that, even when calorie intake is the same between low and high GI diets, low GI diets may improve insulin resistance by increasing insulin sensitivity, and may stimulate more weight loss in people with obesity (Brand‐Miller 2002; Juanola‐Falgarona 2014). A higher GI diet may elevate hunger and stimulate regions in the brain associated with rewards and cravings (Lennerz 2013), whereas a low GI diet triggers greater satiety (Chang 2012). Systematic reviews have shown that low GI diets produced greater weight loss in people with overweight or obesity compared to control diets (Brunstein 2016; Zafar 2018).

The steadier postprandial glucose fluctuation resulting from low GI diets reduces glycaemic variability, which has been shown to be a potentially important health indicator. Research has shown that a higher level of glycaemic variability may be an indicator of a higher risk of microvascular complications (Hirsch 2005), and is associated with: cognitive impairment amongst elderly people with type 2 diabetes (Rizzo 2010); physical and emotional distress, which can be related to negative moods and lower health‐related quality of life (Penckofer 2012); and the development of insulin resistance (Blaak 2012). It has also been reported that an elevated GL is directly associated with type 2 diabetes (Salari‐Moghaddam 2019). As GL load increases, it increases the postprandial glucose response. Increased postprandial glucose level is understood to be a risk factor for type 2 diabetes and cardiovascular disease as it triggers oxidative stress, inflammation, and endothelial dysfunction (Blaak 2012). This condition could be overcome by consuming lower GI or GL diets, which have been shown to improve pro‐inflammatory markers and fasting insulin (Brunstein 2016).

Why it is important to do this review

This review is important for several reasons. First, many new randomised controlled trials examining the effects of low GI and GL diets have been published since the first version of the review (Thomas 2007), making an up‐to‐date synthesis of the evidence necessary. Second, this review aimed to synthesise evidence on a wide range of outcomes. Our primary outcomes are change in body weight and BMI, and adverse events – important patient‐relevant outcomes. Our secondary outcomes include other anthropometric measures, glycaemic control measures, insulin action measures, cardiovascular risk factors, and several other outcomes, giving this review a wider scope than other systematic views on the topic (see, for example, Zafar 2018). Third, we aimed to include studies that focused specifically on weight loss as an outcome, in contrast to Zafar 2018, which compared low GI diets with other diets, regardless of whether they had weight loss as a specific aim. Sustainable weight loss is an important measure for weight management in people with overweight or obesity. If alterations in the GI or GL of a diet can increase insulin sensitivity, decrease weight, or decrease poor health outcomes in people with overweight or obesity (including in people with type 2 diabetes and its associated complications), then the use of low GI/GL diets as a primary preventive strategy would have significant health and cost benefits for individuals and communities.

Objectives

To assess the effects of low glycaemic index or low glycaemic load diets on weight loss in people with overweight or obesity.

Methods

Criteria for considering studies for this review

Types of studies

We included parallel randomised controlled trials.

Types of participants

We included males and females of any age who were classified as overweight or obese using validated and specified criteria. We excluded people who were diagnosed with diabetes mellitus. We also excluded pregnant, postpartum, and menopausal women. 

We defined participants with a BMI between 25 kg/m²and 29.9kg/m²as overweight and those with a BMI of 30 kg/m² or greater as obese (WHO 1997).

Types of interventions

We included studies comparing low GI or low GL diets with higher GI or GL diets or any other diet.

Concomitant interventions had to be identical in both the intervention and comparator groups to establish fair comparisons. If a study included multiple arms, we included any arms that met the inclusion criteria for this review.

For the purpose of this review, we defined low GI diets as any diet with a daily GI value of 45 or less (GIF 2017a), and low GL diets as any diet with a daily GL value of 100 or less (GIF 2017b). 

Minimum duration of intervention and follow‐up

We included trials with dietary interventions lasting eight weeks (two months) or longer. The minimum duration of follow‐up was two weeks after the completion of the intervention. We distinguished between short‐term (up to six months), intermediate‐term (six months up to 12 months), and long‐term (12 months or more) follow‐up.

We defined any follow‐up period going beyond the original time frame for the primary outcome measure, as specified in the power calculation of the study's protocol, as an extended follow‐up period (also called 'open‐label extension study') (Buch 2011; Megan 2012).

Exclusion criteria

We excluded studies in which:

• the intervention was only a generalised recommendation to increase the proportion of low GI foods in the diet, or to reduce the GL, without provision of explicit detail;

• the intervention was either not directly supervised or not well‐documented (for example, by using food diaries or providing food);

• a co‐intervention in the experimental group was not also applied to the control group; or

• final outcome measurements for the intervention and comparator groups were not sampled at the same time point.

Types of outcome measures

We planned to include in the review studies that reported at least one primary or secondary outcome measures. If studies reported none of our primary or secondary outcomes, we planned to exclude the study and provide basic information in the ‘Characteristics of studies awaiting classification' table.

We extracted the following outcomes, using the methods and time points specified below.

Primary outcomes

• Anthropometric measures: body weight (kg); body mass index (BMI); BMI adjusted for age

• Adverse events

Secondary outcomes

• Anthropometric measures other than body weight or BMI

• Glycaemic control

• Insulin action

• Cardiovascular risk factors

• Satiety

• Dietary adherence

• Health‐related quality of life

• All‐cause mortality

Method of outcome measurement

• Anthropometric measures of change in body weight and BMI: measured in kg and kg/m², respectively.

• Adverse events: serious and non‐serious adverse events that occurred during or after the intervention but not necessarily caused by it.

• Anthropometric measures other than changes in body weight or BMI: defined as total fat mass, percentage body fat content, fat‐free mass, truncal to peripheral fat ratio, visceral fat, abdominal fat, lean body mass, skinfold thickness, waist‐to‐hip ratio. Measured by validated tools such as dual‐energy X‐ray absorptiometry (DEXA), magnetic resonance imaging (MRI), and bioelectrical impedance analysis (BIA).

• Glycaemic control: fasting plasma glucose, glucose tolerance test, postprandial plasma glucose levels, and HbA1c (glycated haemoglobin or haemoglobin A1c test).

• Insulin action: fasting plasma insulin, homeostatic model assessment for insulin resistance (HOMA‐IR), and quantitative insulin sensitivity check index (QUICKI).

• Cardiovascular risk factors: blood pressure, oxidative stress, inflammation of the endothelium, C‐reactive protein, lipid profile (total cholesterol, high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, and triglycerides (TG)).

• Satiety: evaluated by questionnaires using validated scales, amount of food eaten ad libitum post‐intervention phase, and postprandial plasma glucose levels.

• Dietary adherence: evaluated by food records, food diaries (e.g. 3‐day food records), food choice checklists, computer‐based checks of consumption, or food‐container weigh‐backs.

• Health‐related quality of life: evaluated by validated instruments, such as the 36‐Item Short‐Form Health Survey (SF‐36) and EuroQoL quality of life scale.

• All‐cause mortality: defined as death from any cause.

Timing of outcome measurement

• For non‐serious and serious adverse events and all‐cause mortality: any time after participants were randomised to the intervention/comparator groups.

• For change in body weight and BMI, other anthropometric measures, glycaemic control, insulin action, lipid profile, cardiovascular risk factors (other than lipid profile), satiety, dietary adherence, and health‐related quality of life: at baseline and any time point following a minimum intervention duration of at least two months.

Search methods for identification of studies

Electronic searches

For this update, we used the replacement approach, where the previous review version was used as one source of studies (Lefebvre 2022). In addition, we searched the following sources, placing no restrictions on the language of publication.

• From 1 January 2006 to 25 May 2022:

  • Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO) (searched 25 May 2022);

  • MEDLINE (Ovid MEDLINE ALL 1946 to May 25, 2022) (searched 25 May 2022);

  • CINAHL EBSCO (Cumulative Index to Nursing and Allied Health Literature) (searched 25 May 2022).

• From the inception of each trial register to 25 May 2022:

  • ClinicalTrials.gov (www.clinicaltrials.gov) (searched 25 May 2022);

  • World Health Organization International Clinical Trials Registry Platform (ICTRP) (www.who.int/trialsearch/) (searched 25 May 2022).

We did not include Embase in our search, as RCTs indexed in Embase are now prospectively added to CENTRAL via a highly sensitive screening process (Cochrane 2020).

For detailed search strategies, see Appendix 1.

Searching other resources

We attempted to identify other potentially eligible studies or ancillary publications by searching the reference lists of included studies, systematic reviews, meta‐analyses, and health technology assessment reports. We also contacted the authors of included studies to obtain additional information on the retrieved studies and establish whether we may have missed further trials.

Data collection and analysis

Selection of studies

Two review authors (CK, YSW) independently screened the abstract, title, or both, of every record we retrieved in the literature searches, to determine which studies we should assess further. We obtained the full texts of all potentially relevant records. We resolved disagreements through consensus or by recourse to a third review author (LNM). If we could not resolve a disagreement, we categorised the study as 'awaiting classification' and contacted the study authors for clarification. We present an adapted PRISMA flow diagram (Figure 1) showing the process of study selection (Page 2021). We listed all articles excluded after full‐text assessment in the Characteristics of excluded studies table and provided the reasons for exclusion.

1.

Data extraction and management

We did not use abstracts or conference proceedings for data extraction unless full study data were available from the study authors because these information sources do not fulfil the CONSORT requirements, which consist of "an evidence‐based, minimum set of recommendations for reporting randomised trials" (CONSORT 2020; Scherer 2018). We presented information on abstracts or conference proceedings in Characteristics of studies awaiting classification. We defined grey literature as records detected in ClinicalTrials.gov or the WHO ICTRP.

For studies that fulfilled our inclusion criteria, four review authors (CK, YSW, WTZ, OYBH) independently extracted key information on participants, interventions, and comparators. We extracted the following data from reports.

• Methods

  • Study design

• Participants

  • Inclusion and exclusion criteria

  • Diagnostic criteria

  • Setting

  • Age 

  • Countries/number of centres 

• Interventions and comparisons according to the 'template for intervention description and replication' (TIDieR) checklist (Hoffmann 2014; Hoffmann 2017)

  • Name of the intervention.

  • Why: rationale, theory, or goal of the elements essential to the intervention.

  • What: physical or informational materials used in the intervention / procedures, activities, or processes used in the intervention.

  • Who provided: expertise, background, and specific training given.

  • How: modes of delivery.

  • Where: location where the intervention occurred, including infrastructure and features.

  • When/how much: the number of times the intervention was delivered over a period of time.

  • Tailoring: if personalisation or adaptations were planned.

  • Modifications: during the course of the study.

  • How well: measurements of adherence or fidelity.

• Outcomes

  • Definitions of relevant outcomes in different study reports.

• Duration of the intervention and follow‐up

• Run‐in‐period

• Publication details (language, funding, status, aim of the study)

We reported these data in Characteristics of included studies tables and in summary tables in the main text (see Table 3 and Table 4).

1. Characteristics of included studies (part one).

Study ID	Intervention(s) and comparator(s)	Screened/eligible (N)		Randomised (N)	Analysed for primary outcome (N)	Finishing study (N)	Randomised finishing study (%)	Follow‐up (extended follow‐up)	Description of sample size calculation
Abete 2008	I: lower GI energy‐restricted diet	NR		16	16	NR	NR	8 weeks (52 weeks)	"Sample size was established considering the weight loss as the main variable. Published values for the standard deviation (SD) of weight loss were applied and 2 kg was considered as the potential difference between means of the two interventions. The statistical power was set up at 80%. Therefore, and by applying a p‐value <0.05, the sample size required was a minimum of 14 volunteers per group."
	C: higher GI energy‐restricted diet			16	16	NR	NR
			Total:	32	32	32	100.0%
Armendariz‐Anguiano 2011	I: low GL diet	NR		27	16	16	59.3%	6 months	"Sample size was calculated as N = 30 per group assuming 5 cm of waist circumference at the end of the study with 80% of power and 5% of significance level."
	C: high GL diet			27	8	8	29.6%
			Total:	54	24	24	44.4%
Das 2007	I: low GL diet	365/46		17	14	14	82.4%	12 months	‐
	C: high GL diet			17	15	15	88.2%
			Total:	34	29	29	85.3%
Ebbeling 2007	I: low GL diet	227/73		36	36	36	100.0%	18 months	"The power assessment for the primary end point, body fat percentage, was based on a 2‐sample t test with 36 participants per diet group and a 5% type I error rate. The mean (SD) baseline body fat percentage was 40.6 (5.6) in the sample of 73. Assuming a correlation of 0.9, the projected SD of change was (2 [1−0.9])½ x 5.6=2.5%. The sample size provided 80% power to detect an effect size of 0.67, or 0.67 x 2.5=1.7%."
	C: low‐fat diet			37	37	37	100.0%
			Total:	73	73	73	100.0%
Gardner 2018	I: healthy low‐carbohydrate diet	1057/803		318	304	238	74.8%	12 months	"Based on the original study design, assuming 100 participants in each of the 4 relevant groups (genotype and dietary assignment), and normally distributed values of weight change at 12 months, there was 80% power to detect clinically meaningful differences in treatment effect by genotype (eg, whether dietary assignment had an effect on weight change at 12 months except for those assigned to the low‐carbohydrate diet who have the low‐carbohydrate genotype because such individuals lose 3.2 kg on average). This calculation was based on simulations, and assumed a 2‐sided Wald test conducted at the.05 level of significance."
	C: healthy low‐fat diet			314	305	241	76.8%
			Total:	632	609	479	75.8%
Goss 2013	I: low GL diet	651/69		40	29	29	72.5%	16 weeks	‐
	C: high GL diet			29	27	27	93.1%
			Total:	69	56	56	81.2%
McMillan‐Price 2006	I: high carbohydrate, average protein, low GI foods diet	148/129		32	32	30	93.8%	12 weeks	"Power calculations indicated that 120 subjects (30 in each arm) provided 90% power to detect a 2‐kg difference in body weight change among groups using significance equals 5%."
	C: high carbohydrate, average protein, high GI foods diet			32	32	27	84.4%
	I: higher protein, carbohydrate reduced, low GI foods diet			33	33	28	84.8%
	C: higher protein, carbohydrate reduced, high GI foods diet			32	32	31	96.9%
			Total:	129	129	116	90.0%
Rouhani 2013	I: low GI diet	1024/90		25	19	19	76.0%	10 weeks	"For estimating the sample size, we used a parallel study sample size formula N = 2[(Z1‐α/2 + Z1‐β)2 × S2]/ d2 where type one (a) and type two error (b) were 0.05 and 0.20 (power = 80 %), respectively. Based on a previous study, the variance of low density lipoprotein (LDL) was 1.2. We also considered 1.2 as the difference in the mean (d) of LDL. The formula showed that the current study needed 16 subjects in each group for 80 % of the power of the study."
	C: healthy nutritional recommendations‐based diet			25	22	22	88.0%
			Total:	50	41	41	82.0%
Solomon 2010	I: low GL diet	413/24		12	12	10	83.3%	12 weeks	‐
	C: high GL diet			12	12	12	100.0%
			Total:	24	24	22	91.7%
Venn 2010	I: diet rich in pulses and wholegrains	307/113		56	53	43	76.8%	18 months	"Sample size calculations showed that 40 participants in each group would be sufficient to detect a 3% difference in weight loss between diets using a type 1 error rate of 0.05 with 80% power. We over‐recruited to account for dropouts, aiming to enroll 55 participants into each group."
	C: diet based on the guidelines of the National Heart Foundation of New Zealand			57	55	30	52.6%
			Total:	113	108	73	75.1%

All studies were parallel randomised controlled trials. 
C: comparison; GI: glycaemic index; GL: glycaemic load; I: intervention; NR: not reported

2. Characteristics of included studies (part two).

Study ID	Intervention(s) and comparator(s)	Duration of intervention (duration of follow‐up)	Study period	Country	Ethnic groups  (%)	Sex (% women)	Age (mean/range years (SD))	BMI (mean kg/m2 (SD))
Abete 2008	I: lower GI energy‐restricted diet	8 weeks (52 weeks)	NR	Spain	NR	50	NR	32.8 (4.3)
	C: higher GI energy‐restricted diet				NR	37.5	NR	32.2 (4.4)
Armendariz‐Anguiano 2011	I: low GL diet	6 months	NR	Mexico	NR	66.6	36.9 (9.0)	30.7 (4.0)
	C: high GL diet				NR	67.8	33.8 (8.2)	32.5 (5.9)
Das 2007	I: low GL diet	12 months	March 2002 to December 2004	USA	NR	76.5	35 (6)	27.6 (1.2)
	C: high GL diet				NR	76.5	34 (5)	27.6 (1.6)
Ebbeling 2007	I: low GL diet	18 months	September 2004 to December 2006	USA	White: 56 Non‐white: 44	81	28.2 (3.8)	NR
	C: low fat diet				White: 51 Non‐white: 49	78	26.9 (4.2)	NR
Gardner 2018	I: healthy low‐carbohydrate diet	52 weeks	January 2013 to May 2016	USA	White: 59.9 Hispanic: 20.1 Asian: 9.9 African American: 4.3 American Indian, Alaskan Native, or Pacific Islander: 0 Other: 5.9	58.9	40.2 (6.7)	33.3 (3.4)
	C: healthy low‐fat diet				White: 57.7 Hispanic: 22.0 Asian: 9.8 African American: 3.3 American Indian, Alaskan Native, or Pacific Islander: 1 Other: 6.2	54.8	39.3 (6.8)	33.4 (3.4)
Goss 2013	I: low GL diet	8 weeks	April 2007 to December 2009	USA	European American: 58 African American: 42	55	35.9 (8.4)	32.4 (4.1)
	C: high GL diet				European American: 50 African American: 50	54	34.7 (8.1)	30.9 (4.5)
McMillan‐Price 2006	I: high carbohydrate, average protein diet based on low GI foods	12 weeks	March 2002 to October 2004	Australia	NR	72	30.5 (1.4)	30.6 (0.8)
	C: high carbohydrate, average protein diet based on high GI foods				NR	78	31.8 (1.7)	30.9 (0.6)
	I: higher protein, carbohydrate reduced diet based on low GI foods				NR	79	34.6 (1.5)	32.1 (0.9)
	C: higher protein, carbohydrate reduced diet based on high GI foods				NR	75	30.2 (1.5)	31.3 (0.8)
Rouhani 2013	I: low GI diet	10 weeks	NR	Iran	NR	100	13 to 18	27.97 (0.6)
	C: healthy nutritional recommendations‐based diet				NR	100	13 to 18	28.82 (1.0)
Solomon 2010	I: low GL diet	12 weeks	NR	USA	NR	70	67 (2)	34.9 (1.1)
	C: high GL diet				NR	58.3	64 (1)	34.1 (1.1)
Venn 2010	I: diet rich in pulses and wholegrains	72 weeks	NR	New Zealand	NR	84	42 (11.2)	36.1 (6.5)
	C: diet based on the guidelines of the National Heart Foundation of New Zealand				NR	88	42 (10.3)	34.7 (4.6)

All studies were in community setting. None of the studies reported the duration of the disease, comedications/cointerventions, nor comorbidities. Only Solomon 2010 reported the mean glycosylated haemoglobin A1c (HbA1c) values (SD): Intervention: 5.66 (0.4) and Control: 5.48 (0.5)

C: comparison; GI: glycaemic index; GL: glycaemic load; I: intervention; NR: not reported

We contacted all authors of included studies to enquire whether they were willing to answer questions regarding their studies. We documented these communications. We thereafter sought relevant missing information on the study from the primary study author(s) if required.

Dealing with duplicate and companion publications

In the event of duplicate publications, companion documents, or multiple reports of a primary study, we maximised the information yield by collating all available data, and we used the most complete data set aggregated across all known publications. We listed duplicate publications, companion documents, multiple reports of a primary study, and trial documents of included trials (such as trial registry information) as secondary references under the study ID of the included study.

Data from clinical trials registers

If data from included trials were available as study results in clinical trials registers, such as ClinicalTrials.gov or similar sources, we made full use of this information and extracted the data. If there was also a full publication of the study, we collated and critically appraised all available data. If an included study was marked as 'completed' in a clinical trial register but no additional information (study results or publication, or both) was available, we added this study to the Characteristics of studies awaiting classification table.

Assessment of risk of bias in included studies

Two review authors (CK, WTZ) independently assessed the risk of bias for each included study. We resolved disagreements by consensus or by consulting a third review author (SLWH). In the case of disagreement, we consulted the rest of the review author team and made a judgement based on consensus. If adequate information was unavailable from the study publications, study protocols, or other sources, we contacted the study authors for more detail to request missing data on risk of bias items.

We used the Cochrane risk of bias assessment tool to assign assessments of low, high, or unclear risk of bias (Higgins 2011). We evaluated individual bias items as described in the Cochrane Handbook for Systematic Reviews of Interventions, according to the criteria and associated categorisations contained therein (Higgins 2011).

Summary assessment of risk of bias

We have presented a risk of bias graph (Figure 2) and a risk of bias summary (Figure 3). We distinguished between self‐reported and investigator‐assessed and adjudicated outcome measures. 

2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies (blank cells indicate that the particular outcome was not measured in some studies).

All studies did not report on all‐cause mortality.

3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study (blank cells indicate that the particular outcome was not measured in some studies).

All studies did not report on all‐cause mortality.

We considered the following self‐reported outcomes:

• adverse events;

• dietary adherence;

• satiety;

• health‐related quality of life.

We considered the following outcomes to be investigator‐assessed:

• body weight and other anthropometric measurements;

• adverse events;

• glycaemic control;

• insulin action;

• cardiovascular risk factors;

• all‐cause mortality.

Risk of bias for a study across outcomes

Some risk of bias domains, such as selection bias (sequence generation and allocation sequence concealment), affect the risk of bias across all outcome measures in a study. In case of high risk of selection bias, we marked all endpoints investigated in the associated study as being at high risk. Otherwise, we did not perform a summary assessment of the risk of bias across all outcomes for a study.

Risk of bias for an outcome within a study and across domains

We assessed the risk of bias for an outcome measure by including all entries relevant to that outcome (i.e. both study‐level entries and outcome‐specific entries). We considered low risk of bias to denote a low risk of bias for all key domains, unclear risk to denote an unclear risk of bias for one or more key domains, and high risk to denote a high risk of bias for one or more key domains.

Risk of bias for an outcome across studies and across domains

To facilitate our assessment of the certainty of the evidence for key outcomes, we assessed the risk of bias across studies and domains for the outcomes included in the summary of findings table. We defined the evidence as being at low risk of bias when most information came from studies at low risk of bias, unclear risk of bias when most information came from studies at low or unclear risk of bias, and high risk of bias when a sufficient proportion of information came from studies at high risk of bias.

Measures of treatment effect

When at least two included studies were available for a comparison of a given outcome, we tried to express dichotomous data as a risk ratio (RR) with 95% confidence intervals (CIs). For continuous outcomes measured on the same scale (e.g. weight loss in kg) we estimated the intervention effect using the mean difference (MD) with 95% CIs. For continuous outcomes that measured the same underlying concept (e.g. health‐related quality of life) but used different measurement scales, we calculated the standardised mean difference (SMD). We expressed time‐to‐event data as a hazard ratio (HR) with 95% CIs.

Unit of analysis issues

If more than one comparison from the same study was eligible for inclusion in the same meta‐analysis, we either combined groups to create a single pair‐wise comparison, or we reduced the sample size so that the same participants did not contribute data to the meta‐analysis more than once (splitting the 'shared' group into two or more groups). Although the latter approach offers some solutions for adjusting the precision of the comparison, it does not account for correlation arising from the inclusion of the same set of participants in multiple comparisons (Higgins 2011).  

Dealing with missing data

Where possible, we obtained missing data from the authors of included studies. We carefully evaluated important numerical data, such as screened, randomly assigned participants, as well as intention‐to‐treat, as‐treated and per‐protocol populations. We investigated attrition rates (e.g. dropouts, losses to follow‐up, and withdrawals) and we critically appraised issues concerning missing data and use of imputation methods (e.g. last observation carried forward).

For studies in which the standard deviation (SD) of the outcome was not available at follow‐up or we could not recreate it, we standardised by the mean of the pooled baseline SD from studies that reported this information. Where included studies did not report means and SDs for outcomes, and we did not receive the requested information from study authors, we imputed these values by estimating the mean and the variance from the median, the range, and the size of the sample (Hozo 2005). We investigated the impact of imputation on meta‐analyses by performing sensitivity analyses, and we reported for every outcome which studies had imputed SDs.

Assessment of heterogeneity

In the event of substantial clinical or methodological heterogeneity, we did not report study results as the pooled effect estimate in a meta‐analysis.

We took into account a visual examination of the variability in point estimates and the overlap in confidence intervals. We used the I² statistic to estimate the degree of heterogeneity present amongst the trials in each analysis. If we identified substantial unexplained heterogeneity, we reported it and explored possible causes by prespecified subgroup analysis. We used the rough guide to interpretation of heterogeneity outlined in Chapter 10 of the Cochrane Handbook (Higgins 2011), as follows:

• 0% to 40%: might not be important;

• 30% to 60%: may represent moderate heterogeneity;

• 50% to 90%: may represent substantial heterogeneity;

• 75% to 100%: considerable heterogeneity.

We avoided the use of absolute cutoff values, but interpreted I² in relation to (a) the size and direction of effects, and (b) the strength of evidence for heterogeneity (e.g. P value from the Chi² test, or CI for I²).

Assessment of reporting biases

We assessed selective reporting of results by comparing (where available) the outcomes listed in trials' original protocols to those reported in the final papers. We also searched clinical trial registries for details of the included trials. We contacted the primary investigator(s) of included trials to determine whether they were aware of any relevant unpublished data. We aimed to identify publication bias with the construction of funnel plots, if we had included 10 or more studies investigating a particular outcome. However, there were insufficient trials eligible for pooling in meta‐analysis in the current version of the review. We plan to undertake this analysis in future if we include more trials. 

Data synthesis

We planned to undertake a meta‐analysis only if we judged the participants, interventions, comparisons, and outcomes were sufficiently similar to ensure a clinically meaningful result. Unless good evidence showed homogeneous effects across studies of different methodological quality, we primarily summarised data using a random‐effects model (Wood 2008). We interpreted random‐effects meta‐analyses with due consideration for the whole distribution of effects and presented a confidence interval. We performed statistical analyses according to the statistical guidelines presented in the Cochrane Handbook (Deeks 2022). Presentation of meta‐analyses using forest plots are disaggregated by duration of the studies. 

Subgroup analysis and investigation of heterogeneity

We expected the following characteristics to introduce clinical heterogeneity, and we planned to carry out subgroup analyses for these, including investigation of interactions (Altman 2003).

• Age (children ≤ 18 years old; adults 19 to 59 years old; and older adults ≥ 60 years old)

• Sex (male and female)

• Body mass index (overweight: 25 to 29.9 kg/m²; obese: ≥ 30 kg/m²)

• Duration of the studies (below one year, one year and more)

We used the formal test for subgroup interactions in Review Manager (Review Manager 2020), acknowledging its limitations due to its observational nature and low power to detect differences with fewer than 10 studies per category (Higgins 2011).

Sensitivity analysis

When applicable, we planned to explore the influence of important factors on effect sizes, by performing sensitivity analyses in which we restrict the analyses to the following types of studies:

• published studies;

• studies with low risk of bias, as specified in the Assessment of risk of bias in included studies section;

• very long or large studies, to establish the extent to which they dominate the results.

We used the following filters, if applicable: diagnostic criteria, imputation used, language of publication (English versus other languages), source of funding (industry versus other), or country (depending on data).

Summary of findings and assessment of the certainty of the evidence

We presented the overall certainty of the evidence for each outcome specified below, according to the GRADE approach, which takes into account issues related to internal validity (risk of bias, inconsistency, imprecision, publication bias) and external validity (such as directness of results). Two review authors (LNM, CK) independently rated the certainty of the evidence for each outcome. We resolved any differences in assessment by discussion or by consultation with a third review author (LS).

If meta‐analysis was not possible, we presented the results in a narrative format in the summary of findings tables. We have justified all decisions to downgrade the certainty of the evidence by using informative footnotes, and we used GRADE guidelines for informative statements (Santesso 2020).

Summary of findings tables

We present summaries of the evidence in Table 1 and Table 2. These provide key information about the best estimate of the magnitude of effect, in relative terms and as absolute differences for each relevant comparison of alternative management strategies; the numbers of participants and studies addressing each important outcome; and a rating of overall confidence in effect estimates for each outcome. We created the summary of findings tables using the methods described in the Cochrane Handbook (Schünemann 2019), along with Review Manager 5 software (Review Manager 2020).

Interventions presented in the summary of findings tables were low GI or GL diet. The comparators were higher GI or GL diet or any other diet.

We reported the following outcomes, listed according to priority:

• anthropometric measures: body mass (kg);

• anthropometric measures: BMI (BMI adjusted for age);

• adverse events;

• health‐related quality of life;

• all‐cause mortality.

Results

Description of studies

Results of the search

For this update, we ran database searches from 1 January 2006 to 25 May 2022 on CENTRAL, MEDLINE, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCO, and from the inception of each trial register to 25 May 2022 on ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (ICTRP). Based on these searches, we identified 3628 records. Three additional records were identified through non‐database sources. After removing duplicate records, 2442 records remained. Based on the screening of titles and abstracts, we excluded 2312 records as not relevant for the review. We obtained the full texts of the remaining 130 records and assessed them for eligibility. We excluded 96 records (73 studies) because they did not meet our inclusion criteria (see Characteristics of excluded studies). We listed five studies as 'awaiting classification'; (Chavez 2017; NCT00940966; NCT01303757; NCT01755962; Slabber 1994), and one study as ongoing (CTRI/2020/11/029252). We included a total of nine new studies (34 records) in this updated review. 

We included one of the studies included in the previous version of the review in this updated version (McMillan‐Price 2006). The other RCTs included in the previous version of the review no longer fulfilled the updated inclusion criteria – specifically, the total daily GI and GL cutoff values – introduced in this update. In addition, since more trials are available now, we excluded short‐term studies, and included only those of at least eight weeks' duration. We listed the Slabber 1994 study as ‘awaiting classification’: we could not determine if the study met the inclusion criteria because we were not able to retrieve any of the authors' contact information. In summary, we included a total of 10 studies in this updated version of this review. 

Included studies

Source of data

All reported data were published in scientific peer‐reviewed journals. We contacted all study authors for additional data. The authors of two studies provided us with additional data (Gardner 2018; Goss 2013).

Comparisons

Seven studies compared lower GI or GL diets with higher GI or GL diets (Abete 2008; Armendariz‐Anguiano 2011; Das 2007; Goss 2013; McMillan‐Price 2006; Solomon 2010; Venn 2010). One of the studies had four arms which were all eligible for inclusion in this review; we compared them in the following way: (a) Arm 2: high carbohydrate/low GI versus Arm 1: high carbohydrate/high GI; and (b) Arm 4: high protein/low GI versus Arm 3: high protein/high GI (McMillan‐Price 2006). 

Three studies compared lower GI or GL diets with any other diets (Ebbeling 2007; Gardner 2018; Rouhani 2013). These other diets consisted of low‐fat diets (Ebbeling 2007; Gardner 2018), and a healthy nutritional recommendations‐based diet (Rouhani 2013).

Overview of study populations

Of the 10 studies, three studies did not provide descriptions of sample size calculation (Das 2007; Goss 2013; Solomon 2010), and two did not provide information on the number of screened/eligible participants (Abete 2008; Armendariz‐Anguiano 2011). A total of 1210 participants were randomised in the included studies. Of these, 612 participants were randomised to low GI or GL diets and 598 participants to comparator groups. All but the Abete 2008 study reported on the number of participants finishing the studies. Finishing rates were 77.7% (463/596) of the participants randomised to low GI or GL diets and 77.3% (450/582) of the participants randomised to comparator groups. The individual sample size across the low GI or Gl diets and comparator groups ranged from 12 participants (Solomon 2010) to 318 participants (Gardner 2018). 

Study design

All included studies were parallel randomised controlled trials. All studies were conducted in single centres. Of the 10 studies, one study was "double‐blinded" (Das 2007), four studies were "single‐blinded" (Ebbeling 2007; Gardner 2018; Goss 2013; Rouhani 2013), one study had no blinding (Venn 2010), and four studies did not report on blinding (Abete 2008; Armendariz‐Anguiano 2011; McMillan‐Price 2006; Solomon 2010). Blinding of outcome accessors was reported in five studies (Das 2007; Ebbeling 2007; Gardner 2018; Goss 2013; Rouhani 2013). Studies were performed from the year 2002 to 2016. The duration of interventions ranged from eight weeks to 18 months. Only one study had an extended follow‐up of 52 weeks (Abete 2008). Two studies reported run‐in periods of seven weeks (Das 2007) and four weeks (Gardner 2018), respectively. No studies were terminated early. 

Settings

All studies were conducted amongst volunteers in community settings. One study included a 3‐day in‐patient stay (Solomon 2010). Five studies were conducted in the USA (Das 2007; Ebbeling 2007; Gardner 2018; Goss 2013; Solomon 2010), one in Australia (McMillan‐Price 2006), one in Iran (Rouhani 2013), one in Mexico (Armendariz‐Anguiano 2011), one in New Zealand (Venn 2010), and one in Spain (Abete 2008).

Participants

Of total participants, 104 were from middle‐income countries (Armendariz‐Anguiano 2011; Rouhani 2013). Three studies reported on the ethnicity of the participants (Ebbeling 2007; Gardner 2018; Goss 2013). Approximately half of the participants in these three studies were White, ranging between 50% (Goss 2013) and 59% (Gardner 2018). One study included only female participants (Rouhani 2013). In the remaining studies, the percentage of female participants ranged from 37.5% to 88.1%. The mean age of study participants ranged from 13 to 67 years old. One study included teenagers only (Rouhani 2013), and one study included older adults only (Solomon 2010). Mean BMI at baseline ranged from 27.6 kg/m² to 36.1 kg/m². One study included aerobic exercise as a co‐intervention (Solomon 2010). No studies reported on comorbidities or comedications used by participants. Major exclusion criteria across studies included: diabetes; uncontrolled hypertension or metabolic disease; renal disease; heart disease; any diseases or medication that could interfere with weight loss; pregnancy; lactation; and low compliance with dietary recommendations. 

Diagnosis

Four studies used the WHO 1997 criteria to classify overweight or obesity (Das 2007; Ebbeling 2007; Goss 2013; McMillan‐Price 2006). One trial used the CDC 2021 criteria for children's overweight and obesity (Rouhani 2013). Two studies used the authors’ preferred cutoff of 28 kg/m² for overweight and obesity (Gardner 2018; Venn 2010); however, there was no indication whether the cutoff was for overweight or obesity. The exact criteria used to diagnose overweight or obesity were unclear for three trials (Abete 2008; Armendariz‐Anguiano 2011; Solomon 2010).  

Interventions

Food provision was reported in five studies (Das 2007; Goss 2013; McMillan‐Price 2006; Solomon 2010; Venn 2010). In Goss 2013 and Solomon 2010, all meals for the participants were provided during the full study period. For Das 2007, all foods were provided for the participants during the first six months and then were self‐prepared by the participants for the following six months. McMillan‐Price 2006 provided carbohydrate and protein foods for the participants to prepare their own meals as well as some preprepared meals. Venn 2010 provided key foods for the first six months and participants consumed their own food for the next 12 months. Below are brief descriptions of the intervention for each included study. 

In Abete 2008, participants were individually instructed to follow the prescribed dietary regime for eight consecutive weeks by a trained dietician within a strict dietary framework, which was repeated on a 3‐day rotation basis. The glycaemic index of the lower GI diet was reduced by counselling individuals to make modifications in their carbohydrate consumption patterns, achieved through advising a focused food selection. Thus, most of the high GI foods in the higher GI diet were replaced by foods with low GI carbohydrates in the lower GI diet.

In Armendariz‐Anguiano 2011, participants received different menus of either low GL or high GL diets, according to randomisation. A research assistant was available by mail or by phone for questions during the 6‐month period. E‐mail, as a reminder and reinforcement to maintain the diet, was sent every two weeks to all participants. All participants completed 3‐day dietary intake diaries at the baseline period and during the third and sixth months. 

In Das 2007, there was a 24‐week calorie restriction phase (six months) during which participants were randomly assigned to a diet with a low GL or a high GL, and all food was provided at 70% of individual baseline weight‐maintenance energy requirements. This was followed by a 24‐week calorie restriction phase (six months), during which participants were instructed to take overall responsibility for food preparation and to continue their low GL or high GL regimen. During the second six months of the study, participants were instructed to self‐select and prepare their own food at home to maintain their randomisation. To prepare for this phase, participants worked with the study dietician to develop an individualised plan that included menus, recipes, portion sizes, and food lists consistent with their randomised diets, prescribed calorie levels, and food preferences. Food scales were provided to help with appropriate portioning, and participants joined a preparatory grocery store tour and cooking class

In Ebbeling 2007, for the low GI diet arm, registered dieticians provided information during cooking demonstrations to encourage the consumption of low GL foods and led interactive activities using food models to define appropriate serving sizes of high GL foods. For the low‐fat diet arm, dieticians encouraged the consumption of low‐fat foods during cooking demonstrations and led interactive activities using food models to define appropriate serving sizes of high‐fat foods. 

In Gardner 2018, participants were instructed to reduce their intake of total fat or digestible carbohydrates to 20 g/day during the first eight weeks. Then individuals slowly added fats or carbohydrates back to their diets in increments of 5 g to 15 g per day per week until they reached the lowest level of intake they believed could be maintained indefinitely. Classes were led by five registered dietician health educators who each taught one healthy low‐fat class and one healthy low‐carbohydrate class per cohort. Dieticians were blinded to all laboratory measures and genotypes.

In Goss 2013, the dietary intervention included two phases: eight weeks under eucaloric conditions followed by eight weeks under hypocaloric conditions. For the duration of the intervention, participants reported to the general clinical research centre each weekday morning to be weighed, eat breakfast, and collect food for their remaining meals. On Fridays, participants picked up food for Saturday and Sunday to consume at home. 

In McMillan‐Price 2006, participants were given eating plans devised to help them lose weight (providing approximately 1400 kcal [6000 kJ] for women and 1900 kcal [8000 kJ] for men) and achieve the desired macronutrient distribution. To maximise compliance, all key carbohydrate and protein foods and some preprepared meals were provided. A colour‐coded “shop” system (different colours for each diet) with a bar code reader was used, and participants collected foods of low or high GI, red meat portions, and specially prepared frozen meals each week.

In Rouhani 2013, volunteers completed a 1‐day weighed dietary record and a 1‐day physical activity record in weeks 2.5, 5, 7.5 and 10 of the study. The participants completed a 4‐day food record and a 4‐day physical activity record to include one weekend and three weekdays. In individual sessions, records were evaluated and clarified. At each visit, one dietician answered participants’ queries. For assessing biochemical variables, one blood sample was drawn after 12 hours of overnight fasting from each participant at baseline and at the end of week 10. Dietary interventions were comprehensively explained to the adolescent participants and their parents. All the meals were provided by parents.

In Solomon 2010, diets were designed by a registered dietician and all meals for the 12‐week intervention were provided to participants. Every session of exercise was fully supervised by an exercise physiologist.

In Venn 2010, cereals and bread provided to the intervention group tended to be of low glycaemic index (< 55), whereas the control group received more refined cereals and breads that tended to be medium to high glycaemic index. Some flexibility was seen with each diet in the food items provided, to accommodate individual preference and to allow for variety. During the first six months, participants attended cooking classes and supermarket tours, and they received dietary advice and recipe cards developed by a registered dietician. Every two weeks, participants attended dietary counselling sessions in pairs, during which they were weighed and received dietary advice from a registered dietician. Participants were encouraged to exercise for half an hour a day and were given a pedometer.

Outcomes

All 10 included studies explicitly stated the endpoints for primary and secondary outcomes. The most frequently defined primary outcome in the studies was weight change. Four studies reported adverse events (Armendariz‐Anguiano 2011; Das 2007; Ebbeling 2007; Gardner 2018). No studies investigated all‐cause mortality.

Excluded studies

We excluded 96 records (73 studies) after full‐text evaluation. Of these, 14 studies had daily diet GI and GL above the cutoff; 13 studies had a duration of fewer than eight weeks; 13 studies' interventions were not related to GI or GL; 12 studies had a BMI inclusion criterion below cutoff; six studies were intended for weight maintenance; six studies had different co‐interventions in the study arms; five studies did not evaluate daily GI or GL; three studies had no data available and were terminated; and one study had a comparator group that was not randomised (see Characteristics of excluded studies).

Ongoing studies

We identified one ongoing trial comparing a low GI diet with standard treatment (CTRI/2020/11/029252). The study plans to include 100 children with overweight or obesity between the ages of nine and 16 years. The primary outcome of the study is a reduction of BMI by 1 kg/m². The duration of the study is estimated to be six months (see Characteristics of ongoing studies).

Studies awaiting assessment

We classified five trials as awaiting classification (Chavez 2017; NCT00940966; NCT01303757; NCT01755962; Slabber 1994; see Characteristics of studies awaiting classification). 

Three of the studies were trials registered under https://clinicaltrials.gov/ and were marked as completed (NCT00940966; NCT01303757; NCT01755962). We contacted the investigators for each trial, but only the investigator of trial NCT01303757 replied, stating that the manuscript for publication has not been completed due to the COVID‐19 pandemic and other issues. The estimated total number of participants from these trials is 283, with an age range from 13 to 40 years old. Trials were conducted between the years 2006 and 2017, with a minimum duration of 12 weeks and a maximum of 18 months. 

One study was published as a conference abstract (Chavez 2017). The author contacted stated that the full manuscript for publication has not been completed. The study compared the effects of a modified carbohydrate diet with a standard proportion of macronutrient diet in a group of women of reproductive age with overweight. 

We reclassified one study included in the previous version of the review as 'awaiting classification', as it was not possible to clarify if the study meets the revised inclusion criteria of this updated review (Slabber 1994). We were unable to contact the researchers of the study. The study compared the effects of a low insulin response diet with a conventionally balanced diet in 40 females with obesity and hyperinsulinaemia.

For further details of the study selection process, see Figure 1.

Risk of bias in included studies

For details on the risk of bias of the included studies, see Characteristics of included studies.

For an overview of our judgements about each risk of bias item for individual studies and across all studies, see Figure 2 and Figure 3. 

Allocation

We judged one study to be at low risk of selection bias for both random sequence generation and allocation concealment (Ebbeling 2007). We judged eight studies to be at low risk of bias regarding random sequence generation and at unclear risk of bias for allocation concealment due to inadequate description of allocation concealment (Abete 2008; Armendariz‐Anguiano 2011; Das 2007; Gardner 2018; McMillan‐Price 2006; Rouhani 2013; Solomon 2010; Venn 2010). We judged one study to be at unclear risk of bias for random sequence generation and allocation concealment as the study gave insufficient descriptions of these (Goss 2013). 

Blinding

The blinding of participants and personnel for nutritional interventions is difficult, if not impossible, in most cases. Thus, we have not judged this domain as a high risk of bias, and rated all studies as having an unclear risk of bias for this domain.

We assessed all included studies to have a low risk of bias for blinding of outcome assessment of anthropometric measures, glycaemic control, insulin action, and cardiovascular risk factors, as we judged that laboratory index measures were unlikely to have been influenced by lack of blinding. We judged all studies to be at high risk of bias for blinding of outcome assessment of adverse events, satiety, dietary adherence, and health‐related quality of life, as these parameters are self‐reported. 

Incomplete outcome data

We judged six studies as having a low risk of attrition bias (Abete 2008; Das 2007; Ebbeling 2007; Gardner 2018; McMillan‐Price 2006; Solomon 2010). In these studies, attrition rates were low (from 0% to 24.2%), balanced in numbers across study arms, and trialists used appropriate methods to handle missing data, such as intention‐to‐treat analysis. 

One study had an overall attrition rate of 18.8%, but dropout was unbalanced between the groups (Goss 2013). The reasons for attrition were not stated, and we judged this study as having an unclear risk of attrition bias. 

We assessed three studies as having a high risk of attrition bias (Armendariz‐Anguiano 2011; Rouhani 2013; Venn 2010). There were imbalanced dropout rates between the study arms, reasons for dropouts were not described, and trialists did not use appropriate methods (such as multiple imputations) to handle missing data. 

Selective reporting

We judged all but one study to have a low risk of reporting bias (Goss 2013). We judged Goss 2013 to have an unclear risk of bias as there was insufficient information. 

Other potential sources of bias

We judged all studies to have a low risk of other bias as none indicated any potential risk of bias from other sources.

Effects of interventions

See: Table 1; Table 2

Low GI or low GL diets compared with higher GI or GL diets

Primary outcomes

Anthropometric measures

Body weight

All included studies reported on change in body weight. Low GI or GL diets may result in little to no difference in body weight change compared to higher glycaemic index or load diets (mean difference (MD) ‐0.82 kg in favour of low GI or GL diets, 95% confidence interval (CI) ‐1.92 to 0.28; I² = 52%; 7 studies, 403 participants; moderate‐certainty evidence; Analysis 1.1). 

1.1. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 1: Body weight (kg)

Subgroup analyses according to duration of the study did not result in differences in body weight change. The effect estimate for studies of less than one year (MD ‐0.63 kg, 95% CI ‐1.84 to 0.58; P = 0.31, I² = 55%; 5 studies, 266 participants) and for studies of one year or more (MD ‐1.58 kg, 95% CI ‐4.69 to 1.54; P = 0.32, I² = 54%; 2 studies, 137 participants) were in favour of low GI or GL diets (Analysis 1.1). Testing for subgroup differences according to age, sex, BMI, or differences in values between GI or GL was not possible due to a lack of data. 

Sensitivity analysis of very long or large studies included the same studies for analysis as that for the subgroup of studies of one year or more. No other sensitivity analyses were possible as the included studies were similar regarding publication status, risk of bias, language, and countries. 

Body mass index (BMI)

Four of the included studies measured change in BMI (Abete 2008; Armendariz‐Anguiano 2011; Solomon 2010; Venn 2010). Low GI or GL diets may result in little to no difference in change in BMI (MD ‐0.45 kg/m² in favour of low GI or GL diets, 95% CI ‐1.02 to 0.12; I² = 22%; 4 studies, 186 participants) with low certainty of evidence (Analysis 1.2). Changes in BMI did not clearly differ between studies with a duration shorter versus longer than one year (Analysis 1.2). We could not perform the remaining subgroup and sensitivity analyses due to the lack of data. 

1.2. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 2: BMI (kg/m ²)

Adverse events

Two studies that assessed adverse events reported no adverse events amongst their participants (Armendariz‐Anguiano 2011; Das 2007). We assessed the certainty of the evidence to be very low. 

Secondary outcomes

Anthropometric measures other than body weight or BMI

Waist circumference

Four studies reported on waist circumference (Abete 2008; Armendariz‐Anguiano 2011; McMillan‐Price 2006; Venn 2010). The pooled evidence suggested that low GI or GL diets may result in little to no difference in changes in waist circumference compared to higher GI or GL diets, with a mean difference of ‐0.49 cm in favour of low GI or GL diets (95% CI ‐1.84 to 0.85; I² = 40%; 4 studies, 293 participants; low‐certainty evidence; Analysis 1.3). Waist circumference did not clearly differ between studies with a duration shorter versus longer than one year (Analysis 1.3). Other subgroup and sensitivity analyses were not possible due to the lack of data.

1.3. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 3: Waist circumference (cm)

Fat mass 

All except one study reported on fat mass (Venn 2010). Low GI or GL diets may result in little to no difference in fat mass (MD ‐0.86 kg in favour of low GI or GL diets, 95% CI ‐1.52 to ‐0.20; I² = 6%; 6 studies, 295 participants; low certainty‐evidence; Analysis 1.4). Fat mass did not clearly differ between studies with a duration shorter versus longer than one year (Analysis 1.4). Further subgroup and sensitivity analysis could not be generated. 

1.4. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 4: Fat mass (kg)

Lean mass

Five studies analysed lean mass (Abete 2008; Armendariz‐Anguiano 2011; Goss 2013; McMillan‐Price 2006; Solomon 2010). The evidence suggested that low GI or GL diets do not increase lean mass (MD 0.28 kg in favour of higher GI or GL diets, 95% CI ‐0.13 to 0.68; I² = 26%; 5 studies, 266 participants; low‐certainty evidence; Analysis 1.5). We did not perform subgroup and sensitivity analyses due to the lack of data. 

1.5. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 5: Lean mass (kg)

Glycaemic control

Fasting blood glucose (FBG) levels

All except one study reported on FBG levels (Goss 2013). The evidence suggests that low GI or GL diets may result in little to no difference in FBG compared to higher GI or GL diets (MD 0.12 mmol/L in favour of higher GI or GL diets, 95% CI 0.03 to 0.21; I² = 0%; 6 studies, 344 participants; low‐certainty evidence; Analysis 1.6). 

1.6. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 6: Fasting blood glucose levels (mmol/L)

HbA1c (glycosylated haemoglobin A1c)

One study reported on HbA1c (Solomon 2010). The authors found an MD of ‐0.27 mmol/L (95% CI –0.74 to 0.20) in favour of low GI or GL diets (1 study, 22 participants; low‐certainty evidence; Analysis 1.7).

1.7. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 7: HbA1c (%)

Insulin action

Fasting plasma insulin

This outcome was reported in five studies (Abete 2008; Armendariz‐Anguiano 2011; Das 2007; McMillan‐Price 2006; Solomon 2010). Low GI or GL diets may have little to no effect on fasting plasma insulin compared to higher GI or GL diets (MD ‐1.93 mmol/L in favour of low GI or GL diets, 95% CI ‐10.10 to 6.25; I² = 54%; 5 studies, 236 participants; low‐certainty evidence; Analysis 1.8). Fasting plasma insulin did not clearly differ between studies with a duration shorter versus longer than one year (Analysis 1.8). 

1.8. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 8: Fasting plasma insulin (pmol/L)

HOMA‐IR (homeostatic model assessment for insulin resistance)

Four of the included studies reported on HOMA‐IR (Abete 2008; Armendariz‐Anguiano 2011; McMillan‐Price 2006; Solomon 2010). Low GI or GL diets may result in little or no difference in HOMA‐IR compared to higher GI or G diets (MD ‐0.21, 95% CI ‐0.47 to 0.04; I² = 21%; 4 studies, 213 participant; low‐certainty evidence; Analysis 1.9). Subgroups and sensitivity analyses were not possible due to the lack of data.

1.9. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 9: HOMA‐IR

Cardiovascular risk factors

Total cholesterol

All except for one study analysed total cholesterol (Goss 2013). Low GI/GL diets may result in little to no difference in total cholesterol compared to higher GI/GL diets (MD 0.10 mmol/L, 95% CI ‐0.28 to 0.48; I² = 93%; 6 studies, 344 participants; low‐certainty evidence; Analysis 1.10). A subgroup analysis according to study duration did not show clear differences for total cholesterol, nor did it offer an explanation for the observed statistical heterogeneity (Analysis 1.10). Other subgroups and sensitivity analyses were not possible due to the lack of data.

1.10. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 10: Total cholesterol (mmol/L)

High‐density lipoprotein (HDL) cholesterol 

All except for one study analysed HDL cholesterol (Goss 2013). Low GI/GL diets may result in little to no differences in HDL cholesterol compared to higher GI/GL diets (MD 0.02 mmol/L in favour of lower GI or GL diets, 95% CI ‐0.02 to 0.07; I² = 0%; 6 studies, 344 participants; low‐certainty evidence; Analysis 1.11). 

1.11. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 11: HDL cholesterol (mmol/L)

Low‐density lipoprotein (LDL) cholesterol

Five studies reported on LDL cholesterol (Abete 2008; Das 2007; McMillan‐Price 2006; Solomon 2010; Venn 2010). The evidence suggests that low GI or GL diets may result in little to no difference in LDL cholesterol (MD ‐0.10 mmol/L in favour of low GI or GL diets, 95% CI ‐0.27 to 0.06; I² = 72%; 5 studies, 321 participants; low‐certainty evidence; Analysis 1.12). 

1.12. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 12: LDL cholesterol (mmol/L)

A subgroup analysis according to study duration suggested a different effect on LDL cholesterol: a mean difference of ‐0.22 mmol/L in favour of low GI or GL diets in studies with interventions lasting under one year (95% CI ‐0.41 to ‐0.03; I² = 67%; 4 studies, 183 participants) and a mean difference of 0.15 mmol/L in favour of higher GI or GL diets in studies with interventions lasting more than one year (95% CI ‐0.15 to 0.46; I² = 60%; 2 studies, 138 participants). However, the subgroup analysis did not offer an explanation for the observed statistical heterogeneity (Analysis 1.12). Further subgroup and sensitivity analyses were not possible. 

Triglycerides

All except one study reported on triglyceride (Goss 2013). Low GI or GL diets may result in no difference in triglyceride compared to higher GI or GL diets (MD 0.00, 95% CI ‐0.08 to 0.08; I² = 0%; 6 studies, 344 participants; low‐certainty evidence; Analysis 1.13).

1.13. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 13: Triglycerides (mmol/L)

Systolic blood pressure

Three studies measured this outcome (Abete 2008; Solomon 2010; Venn 2010). The pooled data suggest that low GI or GL diets may result in little to no difference in systolic blood pressure (MD ‐0.43 mm Hg in favour of low GI or GL diets, 95% CI ‐3.97 to 3.11; I² = 16%; 3 studies, 162 participants; low‐certainty evidence; Analysis 1.14). We did not perform subgroups and sensitivity analyses because there were not enough studies to estimate effects in various subgroups and to test the robustness of the effect measures.

1.14. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 14: Systolic blood pressure (mm Hg)

Diastolic blood pressure

The same three studies that reported on systolic blood pressure also reported diastolic blood pressure. Similarly, low GI or GI diets may result in little to no difference in diastolic blood pressure (MD ‐0.68 mm Hg in favour of low GI or GL diets, 95% CI ‐2.88 to 1.52; I² = 0%; 3 studies, 162 participants; low‐certainty evidence; Analysis 1.15). 

1.15. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 15: Diastolic blood pressure (mm Hg)

Satiety

Satiety was reported in one study (Das 2007). Participants used visual analogue scales to indicate their level of hunger for the day, desire to eat non‐study foods, and satisfaction with the amount of food consumed. At three months, when adherence to the prescribed diets was highest, the desire to eat non‐study foods increased significantly from baseline for both study arms, and the satisfaction with the amount of food provided decreased significantly in the comparator group. Over time, there were no statistically significant differences between the study arms for change in these variables.

Dietary adherence

 All studies but one reported on dietary adherence (Goss 2013). Five studies reported on food provision (Das 2007; Goss 2013; McMillan‐Price 2006; Solomon 2010; Venn 2010), using various tools to measure dietary adherence. These included weighed food record (Abete 2008; Venn 2010), food container weigh‐backs (Das 2007; Solomon 2010), 3‐day dietary record (Armendariz‐Anguiano 2011; McMillan‐Price 2006), daily check sheets (Venn 2010), total energy expenditure (TEE) (Das 2007), and dietary counselling (Solomon 2010).

In Abete 2008, the macronutrients of the study groups were similar; the daily GI index for the lower GI group was between 40 and 45, and between 60 and 65 for the higher GI group. The macronutrients and the daily GI index of the groups were as prescribed. 

In Armendariz‐Anguiano 2011, low versus high GL diets were designed according to the food habits of Mexicans living in Tijuana. Significant reductions (P < 0.05) of energy, carbohydrate, protein, GI, and GL intake were observed in the low GL group after the intervention, whereas only reduction of energy was observed in the high GL group.

Das 2007 reported that participants from both groups were not fully compliant to the diets prescribed and ate more food than was provided or prescribed at any given time during the intervention. 

Participants of the Solomon 2010 study were adherent to the diets prescribed. The daily GI and dietary composition of both groups were as intended. Dietary adherence was 98% ± 1% for the low GI group and 96% ± 1% for the high GI group. 

In McMillan‐Price 2006, analysis of the food diaries showed that all groups achieved their intended carbohydrate and protein distributions with no difference (P > 0.05) in apparent energy intake. And although there was no difference between the two groups in apparent energy intake, exact diet goals for energy distribution were not met.

The intervention group in Venn 2010 was instructed to consume two servings of pulses daily and was provided with lower GI value (< 55) foods in the first six months. As reported, the intervention group consumed an average of 9.9 ± 3.5 servings of pulses per week and had a lower dietary glycaemic index than the control group at two, six, and 12 months. 

Health‐related quality of life

One study reported on the mood states of participants using the mood states questionnaire described in Appendix 2 (Das 2007). Participants rate a series of mood‐related adjectives on a 5‐point scale (ranging from "not at all" to "very strongly"). These adjectives factor into six mood subscales: tension‐anxiety, depression‐dejection, anger‐hostility, vigour‐activity, fatigue‐inertia, and confusion‐bewilderment. While the subscales can be considered individually, it is also possible to calculate a composite total mood disturbance score by summing the individual scores and subtracting the vigour‐activity scores which are reverse‐scored. The overall mean difference in total mood disturbance was ‐3.5 in favour of low GI or GL diets (MD ‐3.5, 95% CI ‐9.33 to 2.33; 42 participants; Analysis 1.16) and was assessed as very low‐certainty evidence. 

1.16. Analysis.

Comparison 1: Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets, Outcome 16: Health‐related quality of life

All‐cause mortality

No study reported on all‐cause mortality.

Low GI or low GL diets compared with any other diet

Primary outcomes 

Anthropometric measures

Body weight 

All studies reported on change in body weight. Low GI or GL diets likely result in little to no difference in body weight change compared to other diets (MD ‐1.24 kg in favour of low GI or GL diets, 95% CI ‐2.82 to 0.34; I² = 70%; 3 studies, 723 participants; moderate‐certainty evidence; Analysis 2.1). 

2.1. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 1: Body weight (kg)

Body weight change did not clearly differ between studies with a duration shorter versus longer than one year. The effect estimates for studies of less than one year (MD ‐0.29 kg, 95% CI ‐1.59 to 1.01; 41 participants) and for studies of one year or more (MD ‐2.37 kg, 95% CI ‐6.15 to 1.41; I² = 83%; 2 studies, 682 participants) were in favour of low GI or GL diets (Analysis 2.1). We did not perform the remaining subgroup and sensitivity analyses due to lack of data. 

Body mass index (BMI)

Two of the included studies measured change in BMI (Rouhani 2013; Gardner 2018). The evidence indicated that low GI or GL diets probably result in little to no difference in change in BMI compared to other diets (MD ‐0.30 kg in favour of low GI or GL diets, 95% CI ‐0.59 to ‐0.01; I² = 0%; 2 studies, 650 participants; moderate‐certainty evidence; Analysis 2.2). 

2.2. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 2: BMI (kg/m²)

Adverse events

Two studies assessed adverse events (Ebbeling 2007; Gardner 2018). The adverse events reported included eating disorders, hypoglycaemia following oral glucose tolerance test, kidney stones, and diverticulitis. The overall certainty of evidence was low. 

One study reported no adverse events at six months and two adverse events at 18 months (Ebbeling 2007). One was not related to the intervention and one, an eating disorder, may have been related to the study (Ebbeling 2007). 

In Gardner 2018, there were 11 adverse events, including hypoglycaemia following oral glucose tolerance test. Gardner 2018 also reported seven serious adverse events requiring hospitalisation, including kidney stones and diverticulitis. The adverse and serious adverse events were equally distributed between the groups.    

Secondary outcomes

Anthropometric measures other than body weight or BMI

Waist circumference

Two studies reported on waist circumference (Gardner 2018; Rouhani 2013). The evidence suggests that low GI or GL diets may result in little to no difference in waist circumference compared to other diets (MD ‐0.72 cm in favour of low GI or GL diets, 95% CI ‐1.95 to 0.51; I² = 0%; 2 studies, 650 participants; low‐certainty evidence; Analysis 2.3). 

2.3. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 3: Waist circumreference (cm)

Fat mass 

No study reported on fat mass.

Lean mass

No study reported on lean mass.

Glycaemic control

Fasting blood glucose (FBG) levels

All studies included FBG as an outcome (Ebbeling 2007; Gardner 2018; Rouhani 2013). The evidence suggests that low GI or GL diets probably do not reduce FBG compared to other diets (MD 0.03 mmol/L in favour of any other diets, 95% CI ‐0.05 to 0.12; I² = 0%; 3 studies, 732 participants; moderate‐certainty evidence; Analysis 2.4).  

2.4. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 4: Fasting blood glucose levels (mmol/L)

HbA1c (glycosylated haemoglobin A1c)

No study reported on HbA1c. 

Insulin action

Fasting plasma insulin

All studies reported on fasting plasma insulin. Low GI or GL diets probably have little to no effect on fasting plasma insulin compared to other diets (MD ‐1.60 pmol/L in favour of low GI or GL diets, 95% CI ‐8.98 to 5.79; I² = 0%; 3 studies, 732 participants; moderate‐certainty evidence; Analysis 2.5).  

2.5. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 5: Fasting plasma insulin (pmol/L)

HOMA‐IR (homeostatic model assessment for insulin resistance)

One study reported on HOMA‐IR (Rouhani 2013). The intervention may lead to little to no difference between the groups at the end of the study period (MD ‐0.35 in favour of low GI or GL diets, 95% CI ‐0.99 to 0.29; 50 participants; low‐certainty evidence; Analysis 2.6). 

2.6. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 6: HOMA‐IR

Cardiovascular risk factors

Total cholesterol

One study reported on total cholesterol (Rouhani 2013). The mean difference was 0.16 mmol/L in favour of any other diets (MD 0.16, 95% CI ‐0.21 to 0.53; 50 participants; low‐certainty evidence; Analysis 2.7). 

2.7. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 7: Total cholesterol (mmol/L)

High‐density lipoprotein (HDL) cholesterol

All studies reported on HDL cholesterol and evidence suggests low GI or GL diets likely result in little to no difference in HDL compared to other diets (MD 0.06 mmol/L in favour of low GI or GL diets, 95% CI 0.04 to 0.09; I² = 0%; 3 studies, 732 participants; moderate‐certainty evidence; Analysis 2.8). 

2.8. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 8: HDL cholesterol (mmol/L)

Low‐density lipoprotein (LDL) cholesterol

All studies included LDL cholesterol as an outcome (Ebbeling 2007; Gardner 2018; Rouhani 2013). Low GI or GL diets probably lead to little to no difference in LDL cholesterol compared to other diets (MD 0.14 mmol/L in favour of any other diets, 95% CI 0.06 to 0.22; I² = 0%; 3 studies, 732 participants; moderate‐certainty evidence; Analysis 2.9). 

2.9. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 9: LDL cholesterol (mmol/L)

Triglycerides

Of the three included studies, only Ebbeling 2007 reported that triglyceride distributions were skewed. Measurements were log‐transformed for analysis to reduce skew and mean change between groups was expressed as a percentage. Therefore, we included data from Ebbeling 2007 in pooled analyses. All three studies reported on triglyceride, and evidence suggests low GI or GL diets probably lead to little to no difference in triglyceride levels compared to any other diets (MD ‐0.19 mmol/L in favour of low GI or GL diets, 95% CI ‐0.29 to ‐0.09; I² = 0%; 3 studies, 732 participants; moderate‐certainty evidence; Analysis 2.10).  

2.10. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 10: Triglycerides (mmol/L)

Systolic blood pressure

All studies had systolic blood pressure as one of their outcomes. Low GI or GL diets likely lead to little to no difference in systolic blood pressure (MD ‐0.29 mm Hg in favour of low GI or GL diets, 95% CI ‐2.54 to 1.96; I² = 41.2%; 3 studies, 723 participants; moderate‐certainty evidence; Analysis 2.11). Systolic blood pressure did not clearly differ between studies with a duration shorter versus longer than one year. The remaining subgroup and sensitivity analyses were not possible due to a lack of data.

2.11. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 11: Systolic blood pressure (mm Hg)

Diastolic blood pressure

Similar to systolic blood pressure, diastolic blood pressure was reported in all included studies and evidence suggests that low GI or GL diets likely result in little or no difference in diastolic blood pressure (MD ‐0.54 mm Hg in favour of low GI or GL diets, 95% CI ‐1.39 to 0.30; I² = 0%; 3 studies, 723 participants; moderate‐certainty evidence; Analysis 2.12). 

2.12. Analysis.

Comparison 2: Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet, Outcome 12: Diastolic blood pressure (mm Hg)

Satiety

No study reported on satiety.

Dietary adherence

All three studies reported dietary adherence, but none reported on food provision. The studies used the following tools to measure dietary adherence: 3‐day dietary record (Ebbeling 2007); 24‐hour multiple‐pass recall interviews (Gardner 2018); and weighed food record and 4‐day dietary record (Rouhani 2013).

Ebbeling 2007 found that, at the end of the intervention, changes in dietary composition differed between the groups as intended. Carbohydrate, GI, and GL reduced in the low GL group, whereas total fat and saturated fat intake reduced in the low fat group. 

In Gardner 2018, all nutrient components were similar for both groups at baseline. As intended, at the end of the intervention, fats and carbohydrates were significantly different (P < 0.001) between the low carbohydrate group and the low fat group. The daily GI and GL were significantly lower (P < 0.001) in the low carbohydrate group. 

Rouhani 2013 defined dietary adherence of the intervention group as achieving daily GI of lower than 50. The 4‐day food records indicated a daily GI value of 42.67 ± 0.07 (mean ± SE), suggesting the intervention group adhered to the diet. 

Health‐related quality of life

No study reported on health‐related quality of life.

All‐cause mortality

No study reported on all‐cause mortality.

Assessment of reporting bias

We did not draw funnel plots due to the limited number of studies per outcome included in the analyses.

Discussion

Summary of main results

This updated review investigated low GI or GL diets compared with higher GI or GL diets or with any other diet. We included 10 studies with a total of 1210 randomised participants. Seven studies compared low GI or GL diets (N = 233) with higher GI or GL diets (N = 222), and three studies compared low GI or GL diets (N = 379) with any other diet (N = 376). One study included adolescents (N = 50), and one study included older adults (N = 24). The duration of the interventions varied from eight weeks to 18 months. We judged no trials to be at low risk of bias on all risk of bias domains.

In comparing low GI or GL diets to higher GI or GL diets for people with overweight or obesity, we observed little to no differences in effect for change in body weight and BMI, with low certainty of evidence. Information on adverse effects was scarce: only two studies evaluated this outcome and reported no events amongst their participants. We judged the certainty of the evidence for this outcome as low. The evidence is very uncertain about the effect of low GI or GL diets on health‐related quality of life. There was no evidence of a difference between low GI or GL diets compared to higher GI or GL diets for all‐cause mortality because no study reported this outcome.

Similarly, comparing low GI or GL diets to any other diet, there was moderate‐certainty evidence of little to no differences between the two groups for change in body weight and BMI. We were unclear whether there were differences in adverse events between low GI or GL diets, because adverse events were not reported separately according to the allocated groups. There was no evidence of a difference between low GI or GL diets and any other diet for health‐related quality of life and all‐cause mortality because no study reported these outcomes. 

Further descriptions of the main outcomes for both comparisons can be found in Table 1 and Table 2. 

For other outcomes, including anthropometric measures other than change in body weight or BMI, glycaemic control, insulin action, and cardiovascular risk factors, we graded the certainty of the evidence as either moderate or low. There were little to no differences in these outcomes when comparing low GI or GL diets with higher GI or GL diets or with any other diets. 

Overall completeness and applicability of evidence

We conducted an extensive search for studies in databases and from non‐database sources, placing no restrictions on language or outcomes reported in studies. We contacted the authors of included studies to obtain additional information relevant to this review. Authors of two studies provided us with additional data (Gardner 2018; Goss 2013). We also handsearched the literature to identify any potential studies to be included in the review. 

In randomised controlled trials (RCTs), selection bias could be present because the participants may be healthier and more motivated than the population from which they are recruited. However, a Cochrane systematic review found that individuals who participated in RCTs had similar clinical outcomes as those who did not (Vist 2008).

Most of the studies were performed in North America. Data on African, Asian, and European countries were lacking. None of the studies was performed in low‐income settings. Currently, there are too few studies to explore the possibility of differences in effect by participant characteristics such as age, sex, and ethnicity/race.

We were strict with our definition of low GI or GL diets and included only studies where the daily GI value was 45 or below, or the daily GL value was 100 or below. This was to ensure consistency of the daily GI and GL values of included studies and to avoid the overlapping of these values between low GI or GL diets with higher GI or GL diets or any other diets. When screening low GI or low GL diets for inclusion in the review, we included studies that had slightly higher GI than the cutoff value but also had a GL value within the cutoff value, and vice versa.

Despite using cutoffs to differentiate low GI or GL diets from their comparator groups, the difference in GI or GL values between low GI or GL diets and the comparator groups of a number of included studies were very small (Armendariz‐Anguiano 2011; Ebbeling 2007; Rouhani 2013; Venn 2010). This may have contributed to the very small differences in outcomes between the compared groups. 

Studies have shown that variation in GL is approximately equally explained by variation in GI and variation in available carbohydrate intake (Livesey 2008). Since GI value is a valid property of foods independent of the individuals’ metabolic status (Lan‐Pidhainy 2011), combining diets with either low GI or low GL is predicted to have similar effect on different outcomes. In addition, a growing body of evidence suggests that diets with a low GI or GL independently decrease the risk of type 2 diabetes, heart disease, and different types of cancer, and offer similar or even higher protection than that seen for whole grains or fibre (Barclay 2008). These findings support the hypothesis that an elevated postprandial glycaemic level may underlie chronic disease, thereby further supporting the combined analysis of studies with low GI or low GL diets in the current review.

The included studies' interventions lasted eight weeks or more. Ideally, we are interested in longer‐term studies for understanding public health significance, since adherence to dietary modification is difficult to maintain. Thus, the public health relevance of trials with short‐term dietary intervention periods in this context is questionable. According to Mirmiran and colleagues (Mirmiran 2021), there are a number of challenges related to nutrition interventions, including the complex nature of these interventions, diverse dietary behaviours, and food cultures. These challenges may have contributed to the limited number of longer‐term nutrition interventions.  

The effectiveness of low GI or GL diets and their comparison groups will be influenced by adherence to dietary patterns. Nine of the 10 included studies reported on dietary adherence. Most of the included studies reported good adherence to the respective dietary advice given or the food provided. However, we were not able to meta‐analyse the results as the reporting methods differed across the studies. 

Certainty of the evidence

We assessed all studies included in this review as having an unclear risk of bias for blinding of participants and personnel due to the nature of the studies. We judged blinding of outcome assessment for dietary adherence as high risk of bias for all studies as this outcome is self‐reported. Thus, results should be interpreted with caution. Table 1 and Table 2 provide GRADE assessment of overall study certainty for each of the two comparisons.

Nine of 10 included studies reported on random sequence generation, and we judged these as having a low risk of selection bias for this domain. The remaining study, Goss 2013, provided insufficient detail on random sequence generation and allocation concealment, so we assessed it as having an unclear risk in both domains. A single study reported on allocation concealment (Ebbeling 2007). We judged all studies as having a low risk of detection bias with regard to anthropometric measure, glycaemic control, insulin action, and cardiovascular risk factors. These outcomes are objective and unlikely to be influenced by a lack of blinding. 

We judged three of the included studies as having a high risk of attrition bias for at least one outcome (Armendariz‐Anguiano 2011; Rouhani 2013; Venn 2010). The main reasons for this judgement were substantial or unbalanced dropout rates, and no report on missing data or handling of missing data. We assessed a single study as having an unclear risk of selective reporting bias (Goss 2013). This was mainly due to not reporting on key outcomes for this review, which we would have expected for this kind of study.

For the comparison of low GI or GL diets with higher GI or GL diets on change in body weight, we downgraded the body of evidence by one level to moderate certainty, for overall risk of bias due to no blinding of participants and study personnel. For change in BMI, we judged evidence certainty to be low, downgrading by one level for risk of bias as there was no blinding of participants and personnel, and one level for imprecision due to the small number of participants. We assessed the evidence certainty for adverse events in this comparison as very low, downgrading by one level for risk of bias due to no blinding of participants and study personnel, and two levels due to the small number of participants and reporting of no events. We rated evidence certainty for health‐related quality of life as very low, downgrading by one level for risk of bias due to no blinding, and two levels for imprecision due to a single study with a wide confidence interval. No studies reported on all‐cause mortality.

For the comparison of low GI or GL diets with any other diets on change in body weight and BMI, we downgraded the certainty of the evidence by one level for overall risk of bias due to no blinding of participants and personnel. We judged adverse events for this comparison as having low‐certainty evidence, downgrading by one level for risk of bias due to no blinding of participants and study personnel, and one level for imprecision as the total events were relatively low and were not reported separately according to comparator groups. No studies for this comparison reported on health‐related quality of life and all‐cause mortality.

Potential biases in the review process

We were unable to conduct meta‐analyses on all outcomes due to the inclusion of only a few trials in most of the comparisons. There were limited or no data available for some outcomes (adverse events, health‐related quality of life, and all‐cause mortality). We were also unable to create funnel plots to evaluate small‐study bias due to an insufficient number of studies for most outcomes. We could perform only a very limited number of sensitivity and subgroup analyses for a subset of outcomes, and these analyses were unable to explain the observed statistical heterogeneity.

We listed five studies as 'awaiting classification'. While most of these studies were recorded as completed in a trial registry or were published as conference abstracts, complete data were either not available or have not been published (Chavez 2017; NCT00940966; NCT01303757; NCT01755962). For these studies, we contacted the investigators for clarification.

Several studies were published in multiple publications, making it difficult to distinguish the primary publication from companion papers in some cases (for more information, see Included studies).

One of the included studies reported endpoints in its study publication that differed from those listed in the trial protocol, contributing to a risk of reporting bias (Goss 2013).

The four review authors who extracted study data were not blinded as to which studies they were extracting data from, which potentially could have biased the review process. However, none of the review authors had any conflict of interest by virtue of involvement in any of the included studies. 

Daily cutoffs of low GI and GL diets were necessary to prevent overlapping of these values across the intervention and comparison diets. However, there is no consensus in the field on these cutoffs. Thus, we adopted the cutoffs suggested by the Glycaemic Index Foundation (GIF 2017a; GIF 2017b), which is directed by academics and supported by the University of Sydney.

Agreements and disagreements with other studies or reviews

Schwingshackl and colleagues conducted two systematic reviews of low GI or GL diets in children and adults with overweight or obesity (Schwingshackl 2013; Schwingshackl 2015). In the review including adults, low GI or GL diets reduced fat‐free mass, C‐reactive protein, and fasting plasma insulin (Schwingshackl 2013). The review that included children and adolescents showed a reduction of triglyceride and HOMA‐IR (Schwingshackl 2015). In our review, however, we could not show that there were clear differences in the main outcomes analysed.

A systematic review by Rouhani 2014 showed that most of the included cross‐sectional studies found that children's obesity is directly linked with GI and GL. This is in agreement with a recent meta‐analysis conducted by Silverii 2022 on the effectiveness of low carbohydrate diets for long‐term weight loss in individuals with obesity. Findings showed that low carbohydrate diets were associated with significant reduction of body weight and BMI at three to four months.

A systematic review by Zafar and colleagues investigated low GI diets as an intervention for obesity (Zafar 2018). They concluded that low GI diets resulted in small but significant improvements in body weight, BMI, LDL cholesterol, and total cholesterol. They included people with normal weight, overweight, and obesity, and individuals with type 2 diabetes. They included 101 studies with 109 study arms. However, they did not collate studies' primary and supplementary publications. Therefore, many studies were included more than once and handled as independent studies. Our review did not include individuals with type 2 diabetes mellitus; a separate Cochrane Review has examined the effects of low GI diets in people with diabetes mellitus (Thomas 2009).

To determine the effect of carbohydrates on the risk of diseases, Hardy 2020 conducted a meta‐analysis amongst participants grouped according to regions in the USA, Europe, and Asia. Findings showed that women with overweight or obesity could shift their carbohydrate intake to higher‐fibre cereal to decrease type 2 diabetes risk, but that higher GL may cancel out this effect. Similarly, Dwivedi 2022 reported that high GI or high GL is associated with an increased risk of cardiovascular disease events, including diabetes, metabolic syndrome, coronary heart disease, stroke, and stroke mortality in the general population. The findings suggested that dietary interventions designed to focus on carbohydrate quality by lowering both GI and GL are recommended for preventing cardiovascular disease outcomes across all populations. 

In contrast to the other reviews described above, we used cutoff points for daily GI and GL values to avoid overlapping of these values between low GI or GL diets and the comparison diets. In this review, we also evaluated dietary adherence, which was not reported in other reviews. None of the other reviews examined health‐related quality of life. 

Authors' conclusions

Implications for practice.

There was no clear evidence about whether low glycaemic index (GI) or glycaemic load (GL) diets have any benefit or harm for our main outcomes (change in body weight and body mass index (BMI), adverse events, health‐related quality of life, and all‐cause mortality) compared with higher GI or GL diets or with any other diet. Similarly, no clear differences were observed for all other outcomes. The results of this review should be treated with caution as the certainty of the evidence is low. 

Implications for research.

There remain uncertainties regarding the effects of low GI or GL diets on health outcomes, indicating that the effect estimates are likely to change with further research. We recommend more well‐powered randomised controlled trials with adequate blinding of outcome assessors to improve the certainty of evidence. In particular, the method of reporting dietary adherence to low GI or GL diets should be standardised. There is a gap in research on patient‐important outcomes, such as health‐related quality of life, reported by only a single study in this review. Furthermore, studies including people from a wide range of ethnicities and with a wide range of dietary habits, as well as studies in low‐ and middle‐income countries, are needed.  

What's new

Date	Event	Description
22 June 2023	New citation required and conclusions have changed	The current version includes additional evidence and clearer conclusions on the evidence.
22 June 2023	New search has been performed	This review is an update of the review first published in Issue 3, 2007. We retained only one study from the original review in this review update due to revisions to the definition of low GI or GL diets and the duration of eligible interventions. We found nine additional new studies and therefore established a database of 10 included studies. The updated search was carried out in May 2022.

History

Protocol first published: Issue 1, 2005
Review first published: Issue 3, 2007

Date	Event	Description
2 November 2008	Amended	Converted to new review format.

Notes

‐

Appendices

Appendix 1. Search strategies

Cochrane Central Register of Controlled Trials (Cochrane Register of Studies Online)

1. MESH DESCRIPTOR Obesity

2. MESH DESCRIPTOR Overweight

3. MESH DESCRIPTOR Weight Loss

4. overweight:TI,AB,KY

5. obes*:TI,AB,KY

6. (weight loss OR weight control):TI,AB,KY

7. (reduc* ADJ5 weight):TI,AB,KY

8. (body mass index ADJ5 25):TI,AB,KY

9. (body mass index ADJ5 30):TI,AB,KY

10. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9

11. MESH DESCRIPTOR Glycemic Index

12. MESH DESCRIPTOR Glycemic Load

13. (low ADJ6 (glycemic index or glycaemic index or glycaemic load or glycemic load)):TI,AB,KY

14. (diet? ADJ6 (glycemic index or glycaemic index or glycaemic load or glycemic load)):TI,AB,KY

15. (food? ADJ6 (glycemic index or glycaemic index or glycaemic load or glycemic load)):TI,AB,KY

16. (diet? ADJ6 (low energy or low insulin or energy restricted or low carb*)):TI,AB,KY

17. #11 OR #12 OR #13 OR #14 OR #15 OR #16

18. #10 AND #17

19. 2006 TO 2020:YR

20. #18 AND #19

MEDLINE (Ovid)

1. Obesity/

2. Overweight/

3. Weight Loss/

4. overweight.tw.

5. obes*.tw.

6. (weight loss or weight control).tw.

7. (reduc* adj5 weight).tw.

8. (body mass index adj5 25).tw.

9. (body mass index adj5 30).tw.

10. or/1‐9

11. Glycemic Index/

12. Glycemic Load/

13. (low adj6 (glycemic index or glycaemic index or glycaemic load or glycemic load)).tw.

14. (diet? adj6 (glycemic index or glycaemic index or glycaemic load or glycemic load)).tw.

15. (food? adj6 (glycemic index or glycaemic index or glycaemic load or glycemic load)).tw.

16. (diet? adj6 (low energy or low insulin or energy restricted or low carb*)).tw.

17. or/11‐16

[Cochrane Handbook 2019 RCT filter ‐ sensitivity max. version – without “drug therapy.fs”]

18. randomized controlled trial.pt.

19. controlled clinical trial.pt.

20. randomi?ed.ab.

21. placebo.ab.

22. randomly.ab.

23. trial.ab.

24. groups.ab.

25. or/18‐24

26. exp animals/ not humans/

27. 25 not 26

28. 10 and 17

29. 28 and 27

30. (2006* or 2007* or 2008* or 2009* or 201* or 202*).dt.

31. 29 and 30

CINAHL (Ebscohost)

1. MH "Obesity+"

2. MH "Weight Loss"

3. TX (overweight OR obes*)

4. TX ("weight loss" OR "weight control")

5. TX (reduc* N5 weight)

6. TX ("body mass index" N5 25)

7. TX ("body mass index" N5 30)

8. S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7

9. MH "Glycemic Index"

10. MH "Glycemic Load"

11. TX (low N6 ("glycemic index" OR "glycaemic index" OR "glycaemic load" OR "glycemic load"))

12. TX (diet# N6 ("glycemic index" OR "glycaemic index" OR "glycaemic load" OR "glycemic load"))

13. TX (food# N6 ("glycemic index" OR "glycaemic index" OR "glycaemic load" OR "glycemic load"))

14. TX (diet# N6 ("low energy" or "low insulin" or "energy restricted" or "low carb*"))

15. S9 OR S10 OR S11 OR S12 OR S13 OR S14

16. S8 AND S15

[S17: Wong 2006 "therapy studies" filter ‐ SDSSGS version]

17. MH "treatment outcomes+" OR MH "experimental studies+" OR random*

18. S17 AND S16

19. S17 AND S16 ‐ Limiters ‐ Published Date: 20060101‐20201231

WHO ICTRP Search Portal (Standard search)

overweight* AND glycemic* OR

overweight* AND glycaemic* OR

obes* AND glycemic* OR

obes* AND glycaemic*

ClinicalTrials.gov (Advanced search)

Conditions: overweight OR obese OR obesity OR "weight loss" OR "weight reduction"

Interventions: ("glycemic index" OR "glycaemic index" OR "glycaemic load" OR "glycemic load" or "low carb" OR "low carbohydrate" OR "low carbohydrates" OR "low energy" or "low insulin" or "energy restricted") AND (diet OR diets OR food OR foods)

Appendix 2. Health‐related quality of life: instruments

Instrument	Dimensions (subscales) (no. of items)	Validated instrument	Answer options	Scores	Minimum score Maximum score	Weighting of scores	Direction of scales	Minimal important difference
Profile of Mood States (POMS) questionnaire   Employed in: Das 2007	Tension‐anxiety Depression‐dejection Anger‐hostility Vigor‐activity Fatigue‐inertia  Confusion‐bewilderment	Yes	5‐point scale; from "0 = not at all" to "4 = very strong" for the period of the "past week, including today". The subscale of vigor‐activity is reverse scored, from "0 = very strong" to "4 = not at all"	Scores for Total Mood Disturbance (add the scores of the five subscales Tension, Depression, Anger, Fatigue, Confusion together and subtract the Vigor score)	Minimum score for all subscales: 0 Maximum score for all subscales: 4	Not reported	Higher values on the subscales imply a greater disturbed mood.  The Vigor subscale is reverse scored.	Not reported

Appendix 3. Selection bias decisions

Selection bias decisions for studies that reported unadjusted analyses: comparison of results obtained using method details alone versus results obtained using method details and study baseline informationa
Reported randomisation and allocation concealment methods	Risk of bias judgement using methods reporting	Information gained from study characteristics data	Risk of bias using baseline information and methods reporting
Unclear methods	Unclear risk	Baseline imbalances present for important prognostic variable(s)	High risk
		Groups appear similar at baseline for all important prognostic variables	Low risk
		Limited or no baseline details	Unclear risk
Would generate a truly random sample, with robust allocation concealment	Low risk	Baseline imbalances present for important prognostic variable(s)	Unclear riskb
		Groups appear similar at baseline for all important prognostic variables	Low risk
		Limited baseline details, showing balance in some important prognostic variablesc	Low risk
		No baseline details	Unclear risk
Sequence is not truly randomised or allocation concealment is inadequate	High risk	Baseline imbalances present for important prognostic variable(s)	High risk
		Groups appear similar at baseline for all important prognostic variables	Low risk
		Limited baseline details, showing balance in some important prognostic variablesc	Unclear risk
		No baseline details	High risk
aTaken from Corbett 2014; judgements highlighted in bold indicate situations in which the addition of baseline assessments would change the judgement about risk of selection bias compared with using methods reporting alone. bImbalance was identified that appears likely to be due to chance. cDetails for the remaining important prognostic variables are not reported.

Data and analyses

Comparison 1. Low glycaemic index (GI) or low glycaemic load (GL) diets versus higher GI or GL diets.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Body weight (kg)	7	403	Mean Difference (IV, Random, 95% CI)	‐0.82 [‐1.92, 0.28]
1.1.1 Intervention less than one year	5	266	Mean Difference (IV, Random, 95% CI)	‐0.63 [‐1.84, 0.58]
1.1.2 Intervention of one year or more	2	137	Mean Difference (IV, Random, 95% CI)	‐1.58 [‐4.69, 1.54]
1.2 BMI (kg/m 2)	4	186	Mean Difference (IV, Random, 95% CI)	‐0.45 [‐1.02, 0.12]
1.2.1 Intervention less than one year	3	78	Mean Difference (IV, Random, 95% CI)	‐0.28 [‐1.19, 0.64]
1.2.2 Intervention of one year or more	1	108	Mean Difference (IV, Random, 95% CI)	‐0.70 [‐1.65, 0.25]
1.3 Waist circumference (cm)	4	293	Mean Difference (IV, Random, 95% CI)	‐0.49 [‐1.84, 0.85]
1.3.1 Intervention less than one year	3	185	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐1.50, 1.31]
1.3.2 Intervention of one year or more	1	108	Mean Difference (IV, Random, 95% CI)	‐2.00 [‐4.35, 0.35]
1.4 Fat mass (kg)	6	295	Mean Difference (IV, Random, 95% CI)	‐0.86 [‐1.52, ‐0.20]
1.4.1 Intervention less than one year	5	266	Mean Difference (IV, Random, 95% CI)	‐0.83 [‐1.59, ‐0.07]
1.4.2 Intervention of one year or more	1	29	Mean Difference (IV, Random, 95% CI)	‐1.12 [‐3.90, 1.66]
1.5 Lean mass (kg)	5	266	Mean Difference (IV, Random, 95% CI)	0.28 [‐0.13, 0.68]
1.6 Fasting blood glucose levels (mmol/L)	6	344	Mean Difference (IV, Random, 95% CI)	0.12 [0.03, 0.21]
1.6.1 Intervention less than one year	4	207	Mean Difference (IV, Random, 95% CI)	0.12 [0.02, 0.23]
1.6.2 Intervention of one year or more	2	137	Mean Difference (IV, Random, 95% CI)	0.15 [‐0.18, 0.49]
1.7 HbA1c (%)	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
1.8 Fasting plasma insulin (pmol/L)	5	236	Mean Difference (IV, Random, 95% CI)	‐1.93 [‐10.10, 6.25]
1.8.1 Intervention less than one year	4	207	Mean Difference (IV, Random, 95% CI)	‐1.53 [‐11.94, 8.88]
1.8.2 Intervention of one year or more	1	29	Mean Difference (IV, Random, 95% CI)	‐4.68 [‐13.88, 4.52]
1.9 HOMA‐IR	4	213	Mean Difference (IV, Random, 95% CI)	‐0.21 [‐0.47, 0.04]
1.10 Total cholesterol (mmol/L)	6	344	Mean Difference (IV, Random, 95% CI)	0.10 [‐0.28, 0.48]
1.10.1 Intervention less than one year	4	207	Mean Difference (IV, Random, 95% CI)	0.07 [‐0.69, 0.83]
1.10.2 Intervention of one year or more	2	137	Mean Difference (IV, Random, 95% CI)	0.15 [‐0.27, 0.58]
1.11 HDL cholesterol (mmol/L)	6	344	Mean Difference (IV, Random, 95% CI)	0.02 [‐0.02, 0.07]
1.11.1 Intervention less than one year	4	207	Mean Difference (IV, Random, 95% CI)	0.01 [‐0.05, 0.06]
1.11.2 Intervention of one year or more	2	137	Mean Difference (IV, Random, 95% CI)	0.04 [‐0.08, 0.17]
1.12 LDL cholesterol (mmol/L)	5	321	Mean Difference (IV, Random, 95% CI)	‐0.10 [‐0.27, 0.06]
1.12.1 Intervention less than one year	3	183	Mean Difference (IV, Random, 95% CI)	‐0.22 [‐0.41, ‐0.03]
1.12.2 Intervention of one year or more	2	138	Mean Difference (IV, Random, 95% CI)	0.15 [‐0.15, 0.46]
1.13 Triglycerides (mmol/L)	6	344	Mean Difference (IV, Random, 95% CI)	‐0.00 [‐0.08, 0.08]
1.13.1 Intervention less than one year	4	207	Mean Difference (IV, Random, 95% CI)	‐0.00 [‐0.11, 0.11]
1.13.2 Intervention of one year or more	2	137	Mean Difference (IV, Random, 95% CI)	0.00 [‐0.12, 0.12]
1.14 Systolic blood pressure (mm Hg)	3	162	Mean Difference (IV, Random, 95% CI)	‐0.43 [‐3.97, 3.11]
1.15 Diastolic blood pressure (mm Hg)	3	162	Mean Difference (IV, Random, 95% CI)	‐0.68 [‐2.88, 1.52]
1.16 Health‐related quality of life	1		Mean Difference (IV, Random, 95% CI)	Totals not selected

Comparison 2. Low glycaemic index (GI) or low glycaemic load (GL) diets versus any other diet.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Body weight (kg)	3	723	Mean Difference (IV, Random, 95% CI)	‐1.24 [‐2.82, 0.34]
2.1.1 Intervention less than one year	1	41	Mean Difference (IV, Random, 95% CI)	‐0.29 [‐1.59, 1.01]
2.1.2 Intervention of one year or more	2	682	Mean Difference (IV, Random, 95% CI)	‐2.37 [‐6.15, 1.41]
2.2 BMI (kg/m2)	2	650	Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.59, ‐0.01]
2.3 Waist circumreference (cm)	2	650	Mean Difference (IV, Random, 95% CI)	‐0.72 [‐1.95, 0.51]
2.4 Fasting blood glucose levels (mmol/L)	3	732	Mean Difference (IV, Random, 95% CI)	0.03 [‐0.05, 0.12]
2.4.1 Intervention less than one year	1	50	Mean Difference (IV, Random, 95% CI)	0.04 [‐0.26, 0.34]
2.4.2 Intervention of one year or more	2	682	Mean Difference (IV, Random, 95% CI)	0.03 [‐0.06, 0.12]
2.5 Fasting plasma insulin (pmol/L)	3	732	Mean Difference (IV, Random, 95% CI)	‐1.60 [‐8.98, 5.79]
2.5.1 Intervention less than one year	1	50	Mean Difference (IV, Random, 95% CI)	‐10.20 [‐31.87, 11.47]
2.5.2 Intervention of one year or more	2	682	Mean Difference (IV, Random, 95% CI)	‐0.46 [‐8.32, 7.39]
2.6 HOMA‐IR	1	50	Mean Difference (IV, Random, 95% CI)	‐0.35 [‐0.99, 0.29]
2.7 Total cholesterol (mmol/L)	1		Mean Difference (IV, Random, 95% CI)	Totals not selected
2.8 HDL cholesterol (mmol/L)	3	732	Mean Difference (IV, Random, 95% CI)	0.06 [0.04, 0.09]
2.8.1 Intervention less than one year	1	50	Mean Difference (IV, Random, 95% CI)	0.00 [‐0.21, 0.21]
2.8.2 Intervention of one year or more	2	682	Mean Difference (IV, Random, 95% CI)	0.06 [0.04, 0.09]
2.9 LDL cholesterol (mmol/L)	3	732	Mean Difference (IV, Random, 95% CI)	0.14 [0.06, 0.22]
2.9.1 Intervention less than one year	1	50	Mean Difference (IV, Random, 95% CI)	0.10 [‐0.08, 0.28]
2.9.2 Intervention of one year or more	2	682	Mean Difference (IV, Random, 95% CI)	0.15 [0.06, 0.23]
2.10 Triglycerides (mmol/L)	3	732	Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.29, ‐0.09]
2.10.1 Intervention less than one year	1	50	Mean Difference (IV, Random, 95% CI)	0.02 [‐0.85, 0.89]
2.10.2 Intervention of one year or more	2	682	Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.29, ‐0.09]
2.11 Systolic blood pressure (mm Hg)	3	723	Mean Difference (IV, Random, 95% CI)	‐0.29 [‐2.54, 1.96]
2.11.1 Intervention less than one year	1	41	Mean Difference (IV, Random, 95% CI)	1.81 [‐1.69, 5.31]
2.11.2 Intervention of one year or more	2	682	Mean Difference (IV, Random, 95% CI)	‐1.10 [‐3.74, 1.53]
2.12 Diastolic blood pressure (mm Hg)	3	723	Mean Difference (IV, Random, 95% CI)	‐0.54 [‐1.39, 0.30]
2.12.1 Intervention less than one year	1	41	Mean Difference (IV, Random, 95% CI)	0.15 [‐1.48, 1.78]
2.12.2 Intervention of one year or more	2	682	Mean Difference (IV, Random, 95% CI)	‐0.80 [‐1.78, 0.19]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Abete 2008.

Study characteristics
Methods	Study design: parallel randomised controlled trial Number of study centres: 1
Participants	Inclusion criteria: obese adults Exclusion criteria: diabetic, hypertensive, having liver, renal or haematological disease as well as other clinical disorders that could interfere with the weight loss process, weight change higher than 3 kg within three months before the start of the study, participation in another scientific study up to 90 days before, chronic pharmacological therapies, pregnant, under surgical or drug‐related obesity treatments, and alcohol or drug abuse Diagnostic criteria: screening of volunteers by means of medical history, physical examination, and fasting blood profile Setting: community setting/free‐living individuals Age group: adults Country/countries where study was performed: Spain
Interventions	Intervention(s): lower GI energy‐restricted diet 53% of energy as carbohydrates, 17% as proteins, and 30% as fat 84% of total carbohydrates from pasta and legumes Comparator(s): higher GI energy‐restricted diet 53% of energy as carbohydrates, 17% as proteins, and 30% as fat 84% of total carbohydrates from rice and potatoes TIDieR description of the intervention: Brief name: two energy‐restricted diets with different food distributions and GI values on weight loss and energy metabolism in the nutritional treatment of obesity Recipient: "Thirty‐two obese subjects (BMI: 32.5 ± 4.3 kg/m2) were recruited to participate in the study (14 women and 18 men; 36 ± 7 years old). Potential volunteers were contacted through internal and local advertisements."  Why: "Physiological evidences indicate that the consumption of high‐GI meals induce hormonal changes that not only influence the availability of metabolic fuels in the postprandial period, but also may stimulate hunger and inhibit fat oxidation. Indeed, several trials have suggested that low‐GI diets provide specific benefits for weight loss and cardiovascular risk reduction by regulating food intake. Based on the potential role of low‐GI foods in weight control and obesity management, the tested hypothesis was that a hypocaloric diet with a selection of foods decreasing the GI can improve the energy response in the treatment of obesity." What (materials): "Balanced diets were designed to provide the same distribution of macronutrients: 53% of energy as carbohydrates, 17% as proteins and 30% as fat (MFA [monounsaturated fatty acid]: 18.8 ± 1.7%, PFA [polyunsaturated fatty acid]: 3.7 ± 0.3%, SFA [saturated fatty acid]: 5.3 ± 0.6%). Participants were individually instructed to follow the prescribed dietary regime for eight consecutive weeks by a trained dietician within a strict dietary framework, which was repeated on a 3‐day rotation basis (Table 1). The glycemic index of the lower‐GI diet was reduced by counselling some modifications in the carbohydrate consumption patterns, which was achieved by advising a driven food selection, affecting also protein quality, fiber nutritional sources and cooking style. Thus, most of the high‐GI foods in the higher‐GI diet were replaced by foods with low‐GI carbohydrates in the lower‐GI diet (Table 1). Foods considered in the GI adjustment threshold were potatoes, rice, bread, pasta and legumes as well as fish and meat products. This approach provided about 84% of total carbohydrates in the lower‐GI diet from pasta and legumes and 84% of total carbohydrates in higher‐GI diet from rice and potatoes. As mentioned earlier, the protein source was different in both intervention groups. Thus, the animal protein intake was decreased, while the plant protein (legumes/cereals) was accordingly increased in the lower‐GI diet. The protein was mainly of animal origin in the other dietary group (Table 1)." What (procedures): NR Who provided: trained dietician How (mode of delivery; individual or group): face to face. "Participants were individually instructed to follow the prescribed dietary regime" Where: NR When and how much: "Participants were individually instructed to follow the prescribed dietary regime for eight consecutive weeks by a trained dietician…". Based on this, the intervention may have been delivered a single time.  Tailoring: "The induced energy restriction of both hypocaloric diets was ‐30% with respect to the individually measured total energy expenditure specifically calculated from the REE assessed by indirect calorimetry (Deltatrac, Datex‐ Ohmeda, Finland) and corrected by the physical activity level of each participant." Modification of intervention throughout the study: NR Strategies to improve or maintain intervention fidelity: "Volunteers were asked to maintain the same habitual physical activity habits during the intervention period, which was assessed through specific questions during the interviews. Weight loss was monitored weekly by a dietician and the intake was controlled by 3‐day weighted food records (2 weekdays and 1 weekend day). Foods records were performed during the week before the beginning of the intervention (week ‐1) and during the week before the end of the nutritional trial (week +7). These data provided information about baseline intake and the adherence to the prescribed diets." Extent of intervention fidelity: "As designed, macronutrient distribution was similar between both experimental groups (Table 2), fulfilling the accepted recommendations for a healthy diet (carbohydrates: 53%, lipids: 30%, proteins: 17%), but with different daily glycemic index ranges (higher‐GI diet: 60 ‐ 65 vs lower‐GI diet: 40 ‐ 45 units). Also, fiber content was statistically different between diets (Table 2)." Duration of intervention: 8 weeks Duration of follow‐up: 1 year Run‐in period: NR
Outcomes	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: not available Endpoints quoted in publications Primary outcome measure(s): body weight  Secondary outcome measure(s): BMI, waist circumference, fat mass, fat free mass, systolic blood pressure, diastolic blood pressure, total cholesterol, HDL, LDL, triglyceride, fasting insulin, fasting glucose, HOMA‐IR, dietary adherence  Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight  Secondary outcome measure(s): not available Other outcome measures: not available
Study registration	Trial identifier: NR Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English Funding: non‐commercial funding; Government of Navarra Declarations of interest: none to declare Publication status: peer‐reviewed journal
Stated aim of study	Quote: "It was aimed to investigate the effects of two energy‐restricted diets with different food distribution and GI values on weight loss and energy metabolism in the nutritional treatment of obesity."
Notes	Baseline characteristics besides BMI and age of the participants were not described. Contact with study authors: attempted on 23 April 2021; no reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Subjects were enrolled in this prospective study and randomly assigned to one of the two dietary treatments." Comment: randomisation method not stated. However, groups appear to have similar baseline characteristics.
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information about the allocation concealment
Blinding of participants and personnel (performance bias) Anthropometric measures	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of participants and personnel (performance bias) Glycaemic control	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of participants and personnel (performance bias) Insulin action	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of participants and personnel (performance bias) Cardiovascular risk factors	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of participants and personnel (performance bias) Dietary adherence	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of outcome assessment (detection bias) Anthropometric measures	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding
Blinding of outcome assessment (detection bias) Glycaemic control	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding
Blinding of outcome assessment (detection bias) Insulin action	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.”
Blinding of outcome assessment (detection bias) Cardiovascular risk factors	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.”
Blinding of outcome assessment (detection bias) Dietary adherence	High risk	Quote: "intake was controlled by 3‐day weighted food records (2 weekdays and 1 weekend day)." Comment: self‐reported dietary intake
Incomplete outcome data (attrition bias) Anthropometric measures	Low risk	Quote: "Thirty‐two obese subjects (BMI: 32.5 ± 4.3 kg/m2) were recruited to participate in the study..." Comment: no dropouts were reported; all 32 participants were included in the outcome analysis.
Incomplete outcome data (attrition bias) Glycaemic control	Low risk	Quote: "Thirty‐two obese subjects (BMI: 32.5 ± 4.3 kg/m2) were recruited to participate in the study..." Comment: no dropouts were reported; all 32 participants were included in the outcome analysis.
Incomplete outcome data (attrition bias) Insulin action	Low risk	Quote: "Thirty‐two obese subjects (BMI: 32.5 ± 4.3 kg/m2) were recruited to participate in the study..." Comment: no dropouts were reported; all 32 participants were included in the outcome analysis.
Incomplete outcome data (attrition bias) Cardiovascular risk factors	Low risk	Quote: "Thirty‐two obese subjects (BMI: 32.5 ± 4.3 kg/m2) were recruited to participate in the study..." Comment: no dropouts were reported; all 32 participants were included in the outcome analysis.
Incomplete outcome data (attrition bias) Dietary adherence	Low risk	Quote: "Thirty‐two obese subjects (BMI: 32.5 ± 4.3 kg/m2) were recruited to participate in the study..." Comment: no dropouts were reported; all 32 participants were included in the outcome analysis.
Selective reporting (reporting bias)	Low risk	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: not available. Endpoints quoted in publications Primary outcome measure(s): body weight  Secondary outcome measure(s): BMI, waist circumference, fat mass, fat free mass, systolic blood pressure, diastolic blood pressure, total cholesterol, HDL, LDL, triglyceride, fasting insulin, fasting glucose, HOMA‐IR, dietary adherence  Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight  Secondary outcome measure(s): not available Other outcome measures: not available Comment: the study protocol was unavailable, but it was clear that the published reports included all expected outcomes.
Other bias	Low risk	Comment: no other potential sources of bias detected.

Armendariz‐Anguiano 2011.

Study characteristics
Methods	Study design: parallel randomised controlled trial Number of study centres: 1
Participants	Inclusion criteria: overweight or obese adults Exclusion criteria: pregnant, diabetic, have cancer, psychiatric disorders or physical disabilities Diagnostic criteria: NR Setting: community setting/free‐living individuals Age group: adults  Country/countries where study was performed: Mexico
Interventions	Intervention(s): low glycemic load diet Low glycemic load diet designed according to the food habits of Mexicans living in the Tijuana area Comparator(s): high glycemic load diet High glycemic load diet designed according to the food habits of Mexicans living in the Tijuana area TIDieR description of the intervention: Brief name: low GL (LGL) diet versus high GL diet in overweight and obese individuals Recipient: "Fifty‐four adults with overweight or obesity were assigned in two groups: 27 subjects with LGL diet and 27 with high glycemic load (HGL) diet." Why: "LGL diets have shown a decrease in fat mass and significant improvement in insulin sensitivity (HOMA) in obese subjects during a 36‐week period. It has also been observed that, in the Mexican culture, after a 3‐week intervention with appropriate diets in hyperlipidemic subjects, LGI diets decrease TC and low‐density lipoproteins (LDL). However, we have not found long‐term studies analyzing the effect of LGL hypocaloric diets on body composition and insulin sensitivity." What (materials): "Two diets were designed including LGL and HGL diets. GI values of each food were estimated from the tables by Foster‐Powell et al. Daily GL was determined by the product of total dietary carbohydrate (grams) and GI of each food and adjusted to energetic intake using the following formulas: GI = (GI of each food X proportion of total carbohydrate contributed from each food); GL= (GI of each food × grams of total carbohydrate from each food)/1,000 kcal. Diets were designed according to the food habits of Mexicans living in the Tijuana area." What (procedures): "On the first day, subjects received different menus of either LGL or HGL diets, according to the randomization. A research assistant was available by mail or by phone for questions during the 6‐month period. E‐mail, as a reminder and reinforcement to maintain the diet, was sent every 2 weeks to all participants." Who provided: "A research assistant was available by mail or by phone for questions during the 6‐month period."  How (mode of delivery; individual or group): "A research assistant was available by mail or by phone for questions during the 6‐month period. E‐mail, as a reminder and reinforcement to maintain the diet, was sent every 2 weeks to all participants." Where: NR When and how much: "On the first day, subjects received different menus of either LGL or HGL diets, according to the randomization... E‐mail, as a reminder and reinforcement to maintain the diet, was sent every 2 weeks to all participants." Tailoring: "Diets were designed according to the food habits of Mexicans living in the Tijuana area." Modification of intervention throughout the study: NR Strategies to improve or maintain intervention fidelity: "All subjects completed 3‐day dietary intake diaries at the baseline period and during the third and the sixth months." Extent of intervention fidelity: self‐reported GL of the intervention group reduced from 121 ± 86 at baseline to 76 ± 22 at 6 months. Duration of intervention: 6 months Duration of follow‐up: NR Run‐in period: NR
Outcomes	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: Not available Endpoints quoted in publications Primary outcome measure(s):  body weight  Secondary outcome measure(s): waist circumference, BMI, fat mass, fat free mass, fasting glucose, fasting insulin, HOMA‐IR, total cholesterol, HDL, LDL, triglyceride, adverse event, dietary adherence Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight  Secondary outcome measure(s): waist circumference, body fat, total cholesterol, HDL, HOMA‐IR Other outcome measures: not available
Study registration	Trial identifier: NR Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English Funding: NR Declaration of interest: NR Publication status: peer‐reviewed journal
Stated aim of study	Quote: "The aim of this study was to compare the effects of different glycemic load diets on biochemical data and body composition, in overweight and obese subjects, during a 6‐month period."
Notes	Contact with study authors: on 23 April 2021; no reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "There were no significant differences between groups in body composition, biochemical markers and nutrient intake variables." Comment: randomisation method not stated. However, groups appear to have similar baseline characteristics.
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information about the allocation concealment.
Blinding of participants and personnel (performance bias) Anthropometric measures	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of participants and personnel (performance bias) Adverse events	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of participants and personnel (performance bias) Glycaemic control	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of participants and personnel (performance bias) Insulin action	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of participants and personnel (performance bias) Cardiovascular risk factors	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of participants and personnel (performance bias) Dietary adherence	Unclear risk	Comment: insufficient information about the blinding of participants and study personnel.
Blinding of outcome assessment (detection bias) Anthropometric measures	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Glycaemic control	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Insulin action	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Cardiovascular risk factors	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Adverse events	Unclear risk	Comment: insufficient information; it was not clear whether outcome was self‐reported or investigator‐assessed.
Blinding of outcome assessment (detection bias) Dietary adherence	High risk	Quote: "Subjects who completed the 3‐day dietary record (two weekdays and one weekend day) were included in the analysis." Comment: self‐reported dietary intake
Incomplete outcome data (attrition bias) Anthropometric measures	High risk	Quote: "Fifty‐four subjects were analyzed at the beginning of the study. At 3 months, 33 (61%) subjects returned for anthropometric and biochemical measurements (18 with LGL diet and 15 with HGL diet), and at 6 months 24 subjects (44%) completed the dietary intake diaries (16 with LGL diet and 8 with HGL diet) and returned for anthropometric and biochemical measurements." Comment: imbalanced dropout rate between the groups. Reasons for dropouts were not described.
Incomplete outcome data (attrition bias) Glycaemic control	High risk	Quote: "Fifty‐four subjects were analyzed at the beginning of the study. At 3 months, 33 (61%) subjects returned for anthropometric and biochemical measurements (18 with LGL diet and 15 with HGL diet), and at 6 months 24 subjects (44%) completed the dietary intake diaries (16 with LGL diet and 8 with HGL diet) and returned for anthropometric and biochemical measurements." Comment: imbalanced dropout rate between the groups. Reasons for dropouts were not described.
Incomplete outcome data (attrition bias) Insulin action	High risk	Quote: "Fifty‐four subjects were analyzed at the beginning of the study. At 3 months, 33 (61%) subjects returned for anthropometric and biochemical measurements (18 with LGL diet and 15 with HGL diet), and at 6 months 24 subjects (44%) completed the dietary intake diaries (16 with LGL diet and 8 with HGL diet) and returned for anthropometric and biochemical measurements." Comment: imbalanced dropout rate between the groups. Reasons for dropouts were not described.
Incomplete outcome data (attrition bias) Cardiovascular risk factors	High risk	Quote: "Fifty‐four subjects were analyzed at the beginning of the study. At 3 months, 33 (61%) subjects returned for anthropometric and biochemical measurements (18 with LGL diet and 15 with HGL diet), and at 6 months 24 subjects (44%) completed the dietary intake diaries (16 with LGL diet and 8 with HGL diet) and returned for anthropometric and biochemical measurements." Comment: imbalanced dropout rate between the groups. Reasons for dropouts were not described.
Incomplete outcome data (attrition bias) Adverse events	High risk	Quote: "Fifty‐four subjects were analyzed at the beginning of the study. At 3 months, 33 (61%) subjects returned for anthropometric and biochemical measurements (18 with LGL diet and 15 with HGL diet), and at 6 months 24 subjects (44%) completed the dietary intake diaries (16 with LGL diet and 8 with HGL diet) and returned for anthropometric and biochemical measurements." Comment: imbalanced dropout rate between the groups. Reasons for dropouts were not described.
Incomplete outcome data (attrition bias) Dietary adherence	High risk	Quote: "Fifty‐four subjects were analyzed at the beginning of the study. At 3 months, 33 (61%) subjects returned for anthropometric and biochemical measurements (18 with LGL diet and 15 with HGL diet), and at 6 months 24 subjects (44%) completed the dietary intake diaries (16 with LGL diet and 8 with HGL diet) and returned for anthropometric and biochemical measurements." Comment: imbalanced dropout rate between the groups. Reasons for dropouts were not described.
Selective reporting (reporting bias)	Low risk	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: not available Endpoints quoted in publications Primary outcome measure(s): body weight  Secondary outcome measure(s): waist circumference, BMI, fat mass, fat free mass, fasting glucose, fasting insulin, HOMA‐IR, total cholesterol, HDL, LDL, triglyceride, adverse event, dietary adherence Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight  Secondary outcome measure(s): waist circumference, body fat, total cholesterol, HDL, HOMA‐IR Other outcome measures: not available Comment: the study protocol was unavailable, but it was clear that the published reports included all expected outcomes.
Other bias	Low risk	Comment: no other potential sources of bias detected.

Das 2007.

Study characteristics
Methods	Study design: parallel randomised controlled trial Number of study centres: 1
Participants	Inclusion criteria: overweight (BMI 25 to 30 kg/m2) but otherwise healthy men and women aged 24 to 45 years old (women) and 25 to 50 years old (men) Exclusion criteria: high physical activity levels (i.e. participation in sports or training for > 12 hours/week), weight fluctuations ( > 6.8 kg in the past year), inability to complete an accurate 7‐day dietary record (accuracy defined as 70% to 130% of estimated energy requirements), and any disease or medications that might influence the results obtained (including diabetes, cancer, coronary heart disease, endocrine disorders, psychiatric diagnosis, or eating disorder). Diagnostic criteria: normal health‐history questionnaire, blood and urine tests, physical and psychological examinations, and assessment of anticipated lifestyle changes, such as pregnancy or moving out of the area. Setting: community setting/free‐living individuals Age group: adults Gender distribution: females and males Country/countries where study was performed: USA
Interventions	Intervention(s): low GL diet 40% carbohydrate, 30% fat, and 30% protein carbohydrate sources were lower in GI based on published GIs of different foods Comparator(s): high GL diet 60% carbohydrate, 20% fat, and 20% protein TIDieR description of the intervention: Brief name: energy‐restricted diets differing in GL values among overweight individuals Recipient: "The subjects were 34 overweight [body mass index (in kg/m2): 25 – 30] but otherwise healthy men and women aged 24–42 [years] who were recruited through a variety of local advertisements." Why: "Calorie restriction (CR) remains the cornerstone of most weight‐management strategies, but there remains no consensus over the role of dietary macronutrient composition in optimizing long‐term weight loss. In part, the lack of consensus probably reflects the fact that most studies in this area have provided dietary advice, rather than food, with resulting uncertainty in the true extent of dietary change. Thus, additional studies that use more detailed and consistent methods are needed to resolve the effects of different dietary patterns on long‐term weight loss." What (materials): "Two diets approximating the range of current dietary recommendations for healthful macronutrient ranges and containing the Dietary Reference Intakes (DRIs) of micronutrients and essential fatty acids were developed for use in this study at 30% CR relative to baseline energy requirements. Diet compositions are summarized in Table 1 for the HG and LG diets, and a list of actual foods that were provided for each type of diet is included in Appendix A. Both diets had consistent features designed to promote CR, including meeting DRIs for dietary fiber, limited inclusion of high‐energy‐density foods, limited liquid calories, and a relatively high variety of low‐energy‐density foods (eg, fruit and vegetables), and a relatively low variety of high‐energy‐dense foods. The diets differed in the ratio of macronutrients (HG: 60% carbohydrate, 20% fat, and 20% protein; LG: 40% carbohydrate, 30% fat, and 30% protein), and the carbohydrate sources in the LG diet had a lower glycemic index (GI) per published GIs of different carbohydrate sources." What (procedures): "The subjects were expected to visit the research center weekly throughout the study for a variety of activities, including weekly behavioral support groups, individual meetings with the study dietitian, safety monitoring, and outcome testing." Who provided: "the subjects worked with the study dietitian" How (mode of delivery; individual or group): face to face. As diets were tailored according to individuals, it is expected that the intervention was provided individually.  Where: "The study was conducted at the Metabolic Research Unit of the Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University" When and how much: "The subjects were expected to visit the research center weekly throughout the study... [This] year long intervention study included a 7‐wk baseline period (phase 1)… Following phase 1, there was a 24‐wk CR phase (phase 2: 6 months) during which the subjects were randomly assigned to a diet with a low glycemic load (LG) or a high glycemic load (HG), and all food was provided at 70% of individual baseline weight‐maintenance energy requirements. The last phase of the study consisted of a 24‐wk CR phase (phase 3: 6 mo) during which the subjects were instructed to take overall responsibility for food preparation and to continue their phase 2 regimen" Tailoring: "During the second 6 mo of the study, the subjects were instructed to self‐select and prepare their own food at home to maintain their randomization. To prepare for this phase, the subjects worked with the study dietitian to develop an individualized plan that included menus, recipes, portion sizes, and food lists that were consistent with their randomized diets, prescribed calorie levels, and food preferences. Food scales were provided to help with appropriate portioning, and the subjects participated in a preparatory grocery store tour and cooking class." Modification of intervention throughout the study: NR Strategies to improve or maintain intervention fidelity: during the first 6 months of the study, food was provided to the participants. "During the second 6 months of the study, the subjects were instructed to self‐select and prepare their own food at home to maintain their randomization. To prepare for this phase, the subjects worked with the study dietitian to develop an individualized plan that included menus, recipes, portion sizes, and food lists that were consistent with their randomized diets, prescribed calorie levels, and food preferences. Food scales were provided to help with appropriate portioning, and the subjects participated in a preparatory grocery store tour and cooking class." Extent of intervention fidelity: "The subjects were requested to bring back their leftover foods, which were weighed and the amounts recorded on the data recording sheets." Duration of intervention: 1 year Duration of follow‐up: NR Run‐in period: 7 weeks
Outcomes	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: NCT00099099 (clinicaltrials.gov/ct2/show/NCT00099099) Primary outcome measure(s):  body weight Secondary outcome measure(s): body fat, blood glucose, insulin, plasma total cholesterol, triacylglycerol, HDL and LDL, adverse event, hunger and satiety, dietary adherence, health‐related quality of life Other outcome measures: not available Endpoints quoted in publications Primary outcome measure(s): bodyweight Secondary outcome measure(s): body fat, blood glucose, insulin, plasma total cholesterol, triacylglycerol, HDL and LDL, adverse events, hunger and satiety, dietary adherence, health‐related quality of life Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): bodyweight Secondary outcome measure(s): body fat, hunger, satiety, dietary adherence Other outcome measures: not available
Study registration	Trial identifier: NCT00099099 Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English Funding: non‐commercial funding 1) National Institutes of Health (NIH) grant; 2) U.S. Department of Agriculture; 3) Boston Obesity Nutrition Research Center (BONRC) NIH Declaration of interest: none to declare Publication status: peer‐reviewed journal
Stated aim of study	Quote: "The objective was to examine the effects of 2 dietary macronutrient patterns with different glycemic loads on adherence to a prescribed regimen of calorie restriction (CR), weight and fat loss, and related variables"
Notes	Contact with study authors: 11 February 2021: general request for additional study data. Response: 15 February 2021: author was unable to access the research data due to Covid‐19 pandemic.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "A block randomization stratified on body mass index, sex, and diet group was used." Comment: groups appear similar at baseline for all important prognostic variables
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information about the allocation concealment.
Blinding of participants and personnel (performance bias) Anthropometric measures	Unclear risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR [calorie restriction]." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Adverse events	Unclear risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Glycaemic control	Unclear risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Insulin action	Unclear risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Cardiovascular risk factors	Unclear risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Satiety	High risk	Comment: Satiety is self reported.
Blinding of participants and personnel (performance bias) Dietary adherence	Unclear risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Health‐related quality of life	Unclear risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of outcome assessment (detection bias) Anthropometric measures	Low risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR." Comment: blinding of participants and key study personnel was ensured.
Blinding of outcome assessment (detection bias) Satiety	High risk	Comment: satiety is self‐reported.
Blinding of outcome assessment (detection bias) Glycaemic control	Low risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR." Comment: blinding of participants and key study personnel was ensured.
Blinding of outcome assessment (detection bias) Insulin action	Low risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR." Comment: blinding of participants and key study personnel was ensured.
Blinding of outcome assessment (detection bias) Cardiovascular risk factors	Low risk	Quote: "All outcome‐assessment staff were blinded to participant randomization, and the subjects were not informed of their randomization until month 3 of CR." Comment: blinding of participants and key study personnel was ensured.
Blinding of outcome assessment (detection bias) Adverse events	Unclear risk	Comment: insufficient information; it was not clear whether outcome was self‐reported or investigator‐assessed.
Blinding of outcome assessment (detection bias) Health‐related quality of life	High risk	Comment: mood was self‐reported and is subjective to the feelings of participants.
Blinding of outcome assessment (detection bias) Dietary adherence	High risk	Quote: "The subjects were requested to bring back their leftover foods, which were weighed and the amounts recorded on the data recording sheets... Intakes were self‐recorded during these times." Comment: self‐reporting was part of the dietary reporting approach.
Incomplete outcome data (attrition bias) Anthropometric measures	Low risk	Comment: attrition was 3 and 2 participants from the low GL and high GL groups, respectively. Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
Incomplete outcome data (attrition bias) Satiety	Low risk	Comment: attrition was 3 and 2 participants from the low GL and high GL groups, respectively. Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
Incomplete outcome data (attrition bias) Glycaemic control	Low risk	Comment: attrition was 3 and 2 participants from the low GL and high GL groups, respectively. Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
Incomplete outcome data (attrition bias) Insulin action	Low risk	Comment: attrition was 3 and 2 participants from the low GL and high GL groups, respectively. Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
Incomplete outcome data (attrition bias) Cardiovascular risk factors	Low risk	Comment: attrition was 3 and 2 participants from the low GL and high GL groups, respectively. Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
Incomplete outcome data (attrition bias) Adverse events	Low risk	Comment: attrition was 3 and 2 participants from the low GL and high GL groups, respectively. Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
Incomplete outcome data (attrition bias) Health‐related quality of life	Low risk	Comment: attrition was 3 and 2 participants from the low GL and high GL groups, respectively. Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
Incomplete outcome data (attrition bias) Dietary adherence	Low risk	Comment: attrition was 3 and 2 participants from the low GL and high GL groups, respectively. Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups.
Selective reporting (reporting bias)	Low risk	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: NCT00099099 (clinicaltrials.gov/ct2/show/NCT00099099) Primary outcome measure(s): body weight Secondary outcome measure(s): body fat, blood glucose, insulin, plasma total cholesterol, triacylglycerol, HDL and LDL, adverse event, hunger and satiety, dietary adherence, health‐related quality of life Other outcome measures: not available Endpoints quoted in publications Primary outcome measure(s): bodyweight Secondary outcome measure(s): body fat, blood glucose, insulin, plasma total cholesterol, triacylglycerol, HDL and LDL, adverse events, hunger and satiety, dietary adherence, health‐related quality of life Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): bodyweight Secondary outcome measure(s): body fat, hunger, satiety, dietary adherence Other outcome measures: not available Comment: the study protocol was available and all the study's prespecified outcomes that were of interest to this review were reported in the prespecified way.
Other bias	Low risk	Comment: no other potential sources of bias detected.

Ebbeling 2007.

Study characteristics
Methods	Study design: parallel randomised controlled trial Number of study centres: 1
Participants	Inclusion criteria: age 18 to 35 years, BMI of 30 and above, medical clearance from a primary care provider Exclusion criteria: body weight exceeding 140 kg, current smoking, recent adherence to a weight loss diet, use of medications that could affect study outcomes, diabetes mellitus (fasting plasma glucose ≥ 126 mg/dL [7mmol/L] or any other major illness, as assessed by a medical history and laboratory screening tests (blood urea nitrogen, creatine, alanine transaminase, hematocrit) Diagnostic criteria: medical history and laboratory screening tests Setting: community setting/free‐living individuals Age group: adults  Gender distribution: females and males Country/countries where study was performed: USA
Interventions	Intervention(s): low glycemic load diet  40% carbohydrate and 35% fat Comparator(s): low‐fat diet  55% carbohydrate and 20% fat TIDieR description of the intervention: Brief name: a low glycemic load versus a low‐fat diet Recipient: older adults  Why: to determine whether insulin secretion affects weight loss with 2 popular diets What (materials): nutrition education and dietary counselling were provided to participants in both the low glycemic load and low‐fat diet groups. What (procedures): registered dietitians provided information during cooking demonstrations to encourage consumption of low glycemic load foods and led interactive activities using food models to define appropriate serving sizes of high glycemic load foods; to encourage consumption of low‐fat foods and led interactive activities using food models to define appropriate serving sizes of high‐fat foods. Who provided: registered dietitian How (mode of delivery; individual or group): individual and groups. Face to face workshops and motivational telephone calls Where: Boston, MA When and how much: "The same intervention schedule, consisting of a 6‐month intensive intervention period and a 12‐month follow‐up period, was implemented for both groups. There were 23 group workshops (1 hour each), 1 private counseling session (1 hour), and 5 motivational telephone calls (30 minutes each). Six of the group workshops were scheduled during the first 2 months of the intervention period, and the remaining workshops were held on a monthly basis thereafter. The private session occurred during the initial month, and a telephone call was scheduled for each of the subsequent 5 months of the intensive intervention period." Tailoring: "Participant adherence was evaluated based on attendance at group workshops and the private session, completion of motivational telephone calls and self‐reported dietary intake. " Modification of intervention throughout the study: "Dietitians were directive in negotiating goals with participants and empathetic when assisting them in overcoming adherence challenges. Participants were asked to keep one 3‐day food diary prior to each workshop, particularly during the intensive intervention period, as a strategy for monitoring goal attainment. Dietitians prepared written feedback on submitted diaries, highlighting successes and providing advice for correcting deviations from diet presciptions." Strategies to improve or maintain intervention fidelity: "First, group workshops were scripted and written educational materials were developed to ensure delivery of well‐defined nutrition messages for each diet group. Second, flow‐charts provided structure for the private session and motivational telephone calls and were used to foster dietitian adherence to a participant‐centered counseling model, with adequate flexibility for addressing situations unique to each individual. Third, weekly staff meetings provided an opportunity for continued discussion on intervention delivery, particularly strategies for assisting individual participants without compromising differentiation between diets. Fourth, dietitians were given detailed guidelines for providing written feedback on food diaries to avoid unintended overlap in dietary advice between groups." Extent of intervention fidelity: NR Duration of intervention: 18 months  Duration of follow‐up: NR Run‐in period: NR
Outcomes	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: NCT00130299 (clinicaltrials.gov/ct2/show/NCT00130299) Primary outcome measure(s): adiposity Secondary outcome measure(s): HLD, LDL, triglyceride, blood pressure, plasma glucose level, and serum insulin Other outcome measure(s): not available Trial results available in trial register: yes  Endpoints quoted in publications Primary outcome measure(s): body weight, body fat percentage Secondary outcome measure(s): HLD, LDL, triglyceride, blood pressure, plasma glucose level, serum insulin, adverse events, dietary adherence Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight, body fat percentage Secondary outcome measure(s): insulin concentration, HDL, LDL Other outcome measures: not available
Study registration	Trial identifier: NCT00130299 Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English  Funding: other funding: the National Institute of Diabetes and Digestive and Kidney Diseases (Bethesda, Md) (grant R01 DK59240); the Charles H. Hood Foundation (Boston, Mass); and the National Center for Research Resources (Bethesda, Md) to support the General Research Center at Children's Hospital (Boston, Mass) (grant M01 RR02172). Declaration of interest: quote: "Dr Ludwig reported being the author of a book on childhood obesity (Ending the Food Fight: Guide Your Child to a Healthy Weight in a Fast Food/Fake Food World). No other author reported disclosures". Publication status: peer‐reviewed journal
Stated aim of study	Quote: "The purpose of this study was to determine whether insulin secretion affects body fat loss among obese individuals consuming self‐prepared diets. Toward this end, we conducted an 18‐month randomized controlled trial to compare the efficacy of a low– glycemic load/higher‐fat diet with a low‐fat/higher–glycemic load diet."
Notes	Contact with study authors: 25 January 2021: general request for additional study data. Response: 25 June 2021: due to the age of the study, author was unable to provide additional study data.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Enrolled participants were entered sequentially onto a list of random group assignments prepared in advance by the study statistician, with stratification by sex and ethnicity/race (based on participant self‐report of non‐Hispanic white or other)." Comment: sequential numbering based on random group assigment.
Allocation concealment (selection bias)	Low risk	Quote: "The sequence of random assignments was permuted within stratum in blocks of 2 and 4. To avoid any bias in assigning participants to diet groups, staff conducting recruitment and enrollment were masked to sequence. The study director assigned participants to groups. " Comment: sequential numbering with blinding of staff involved in recruitment.
Blinding of participants and personnel (performance bias) Anthropometric measures	Unclear risk	Quote: "A methodological concern with most nutrition‐related outpatient clinical trials is the possibility of bias because study participants consuming self‐prepared diets and the study staff providing education and counseling generally cannot be masked to group assignment. However, we believe that this possibility has been minimized in our study for several reasons. First, considerable effort was made to maintain similar treatment intensity and treatment fidelity between groups. Second, process measures demonstrated that the intended changes in diet occurred in both groups, whereas protein and fiber, 2 potential confounders, did not differ between groups. Third, other process measures showed that physical activity and participant satisfaction also did not differ between groups. Moreover, dietitians delivered the interventions without knowing which individuals were in the low‐concentration and high‐concentration insulin strata at 30 minutes after a dose of oral glucose." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Adverse events	Unclear risk	Quote: "A methodological concern with most nutrition‐related outpatient clinical trials is the possibility of bias because study participants consuming self‐prepared diets and the study staff providing education and counseling generally cannot be masked to group assignment. However, we believe that this possibility has been minimized in our study for several reasons. First, considerable effort was made to maintain similar treatment intensity and treatment fidelity between groups. Second, process measures demonstrated that the intended changes in diet occurred in both groups, whereas protein and fiber, 2 potential confounders, did not differ between groups. Third, other process measures showed that physical activity and participant satisfaction also did not differ between groups. Moreover, dietitians delivered the interventions without knowing which individuals were in the low‐concentration and high‐concentration insulin strata at 30 minutes after a dose of oral glucose." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Glycaemic control	Unclear risk	Quote: "A methodological concern with most nutrition‐related outpatient clinical trials is the possibility of bias because study participants consuming self‐prepared diets and the study staff providing education and counseling generally cannot be masked to group assignment. However, we believe that this possibility has been minimized in our study for several reasons. First, considerable effort was made to maintain similar treatment intensity and treatment fidelity between groups. Second, process measures demonstrated that the intended changes in diet occurred in both groups, whereas protein and fiber, 2 potential confounders, did not differ between groups. Third, other process measures showed that physical activity and participant satisfaction also did not differ between groups. Moreover, dietitians delivered the interventions without knowing which individuals were in the low‐concentration and high‐concentration insulin strata at 30 minutes after a dose of oral glucose." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Insulin action	Unclear risk	Quote: "A methodological concern with most nutrition‐related outpatient clinical trials is the possibility of bias because study participants consuming self‐prepared diets and the study staff providing education and counseling generally cannot be masked to group assignment. However, we believe that this possibility has been minimized in our study for several reasons. First, considerable effort was made to maintain similar treatment intensity and treatment fidelity between groups. Second, process measures demonstrated that the intended changes in diet occurred in both groups, whereas protein and fiber, 2 potential confounders, did not differ between groups. Third, other process measures showed that physical activity and participant satisfaction also did not differ between groups. Moreover, dietitians delivered the interventions without knowing which individuals were in the low‐concentration and high‐concentration insulin strata at 30 minutes after a dose of oral glucose." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Cardiovascular risk factors	Unclear risk	Quote: "A methodological concern with most nutrition‐related outpatient clinical trials is the possibility of bias because study participants consuming self‐prepared diets and the study staff providing education and counseling generally cannot be masked to group assignment. However, we believe that this possibility has been minimized in our study for several reasons. First, considerable effort was made to maintain similar treatment intensity and treatment fidelity between groups. Second, process measures demonstrated that the intended changes in diet occurred in both groups, whereas protein and fiber, 2 potential confounders, did not differ between groups. Third, other process measures showed that physical activity and participant satisfaction also did not differ between groups. Moreover, dietitians delivered the interventions without knowing which individuals were in the low‐concentration and high‐concentration insulin strata at 30 minutes after a dose of oral glucose." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Dietary adherence	Unclear risk	Quote: "A methodological concern with most nutrition‐related outpatient clinical trials is the possibility of bias because study participants consuming self‐prepared diets and the study staff providing education and counseling generally cannot be masked to group assignment. However, we believe that this possibility has been minimized in our study for several reasons. First, considerable effort was made to maintain similar treatment intensity and treatment fidelity between groups. Second, process measures demonstrated that the intended changes in diet occurred in both groups, whereas protein and fiber, 2 potential confounders, did not differ between groups. Third, other process measures showed that physical activity and participant satisfaction also did not differ between groups. Moreover, dietitians delivered the interventions without knowing which individuals were in the low‐concentration and high‐concentration insulin strata at 30 minutes after a dose of oral glucose." Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of outcome assessment (detection bias) Anthropometric measures	Low risk	Quote: "Data collected by personnel who were masked to group assignment." Comment: blinding of outcome assessment is ensured.
Blinding of outcome assessment (detection bias) Glycaemic control	Low risk	Quote: "Data collected by personnel who were masked to group assignment." Comment: blinding of outcome assessment is ensured.
Blinding of outcome assessment (detection bias) Insulin action	Low risk	Quote: "Data collected by personnel who were masked to group assignment." Comment: blinding of outcome assessment is ensured.
Blinding of outcome assessment (detection bias) Cardiovascular risk factors	Low risk	Quoted: "Data collected by personnel who were masked to group assignment. A blood sample was drawn by venipuncture, after a 12‐hour overnight fast, and stored at –80°C until assay for lipids, glucose, and insulin." Comment: based on above information, there is low risk of bias between groups as the personnel who collected data were masked to group assignment.
Blinding of outcome assessment (detection bias) Adverse events	Unclear risk	Comment: insufficient information; it was not clear whether outcome was self‐reported or investigator‐assessed.
Blinding of outcome assessment (detection bias) Dietary adherence	High risk	Quote: "Participants were asked to keep one 3‐day food diary prior to each workshop, particularly during the intensive intervention period" Comment: self‐reported dietary intake
Incomplete outcome data (attrition bias) Anthropometric measures	Low risk	Quote: "Statistical issues include the possibility of bias from use of imputed data, the modest sample size (particularly for analyses involving insulin concentration at 30 minutes at the later time points), and the possibility of “overfitting” too many covariates for the sample size. We do not believe that these concerns threaten the validity of the findings. Our conservative imputation strategy would tend to bias toward the null hypothesis. The SEs were based on pooled variance estimates from the full mixed‐model analysis rather than potential underestimates from predominantly imputed values at the later time points. We included a random effect to take proper account of small‐sample variability. Finally, the degrees of freedom expended on covariate adjustment amounted to a small fraction of the total number of data points, and their omission had negligible effect on the primary statistical tests...We analyzed data using the intention‐to‐treat principle, with conservative methods for imputing missing data." Comment: intention‐to‐treat analysis was used
Incomplete outcome data (attrition bias) Glycaemic control	Low risk	Quote: "Statistical issues include the possibility of bias from use of imputed data, the modest sample size (particularly for analyses involving insulin concentration at 30 minutes at the later time points), and the possibility of “overfitting” too many covariates for the sample size. We do not believe that these concerns threaten the validity of the findings. Our conservative imputation strategy would tend to bias toward the null hypothesis. The SEs were based on pooled variance estimates from the full mixed‐model analysis rather than potential underestimates from predominantly imputed values at the later time points. We included a random effect to take proper account of small‐sample variability. Finally, the degrees of freedom expended on covariate adjustment amounted to a small fraction of the total number of data points, and their omission had negligible effect on the primary statistical tests...We analyzed data using the intention‐to‐treat principle, with conservative methods for imputing missing data." Comment: intention‐to‐treat analysis was used
Incomplete outcome data (attrition bias) Insulin action	Low risk	Quote: "Statistical issues include the possibility of bias from use of imputed data, the modest sample size (particularly for analyses involving insulin concentration at 30 minutes at the later time points), and the possibility of “overfitting” too many covariates for the sample size. We do not believe that these concerns threaten the validity of the findings. Our conservative imputation strategy would tend to bias toward the null hypothesis. The SEs were based on pooled variance estimates from the full mixed‐model analysis rather than potential underestimates from predominantly imputed values at the later time points. We included a random effect to take proper account of small‐sample variability. Finally, the degrees of freedom expended on covariate adjustment amounted to a small fraction of the total number of data points, and their omission had negligible effect on the primary statistical tests...We analyzed data using the intention‐to‐treat principle, with conservative methods for imputing missing data." Comment: intention‐to‐treat analysis was used
Incomplete outcome data (attrition bias) Cardiovascular risk factors	Low risk	Quote: "Statistical issues include the possibility of bias from use of imputed data, the modest sample size (particularly for analyses involving insulin concentration at 30 minutes at the later time points), and the possibility of “overfitting” too many covariates for the sample size. We do not believe that these concerns threaten the validity of the findings. Our conservative imputation strategy would tend to bias toward the null hypothesis. The SEs were based on pooled variance estimates from the full mixed‐model analysis rather than potential underestimates from predominantly imputed values at the later time points. We included a random effect to take proper account of small‐sample variability. Finally, the degrees of freedom expended on covariate adjustment amounted to a small fraction of the total number of data points, and their omission had negligible effect on the primary statistical tests...We analyzed data using the intention‐to‐treat principle, with conservative methods for imputing missing data." Comment: intention‐to‐treat analysis was used
Incomplete outcome data (attrition bias) Adverse events	Unclear risk	Comment: insufficient information
Incomplete outcome data (attrition bias) Dietary adherence	Low risk	Quote: "Statistical issues include the possibility of bias from use of imputed data, the modest sample size (particularly for analyses involving insulin concentration at 30 minutes at the later time points), and the possibility of “overfitting” too many covariates for the sample size. We do not believe that these concerns threaten the validity of the findings. Our conservative imputation strategy would tend to bias toward the null hypothesis. The SEs were based on pooled variance estimates from the full mixed‐model analysis rather than potential underestimates from predominantly imputed values at the later time points. We included a random effect to take proper account of small‐sample variability. Finally, the degrees of freedom expended on covariate adjustment amounted to a small fraction of the total number of data points, and their omission had negligible effect on the primary statistical tests...We analyzed data using the intention‐to‐treat principle, with conservative methods for imputing missing data." Comment: intention‐to‐treat analysis was used
Selective reporting (reporting bias)	Low risk	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: NCT00130299 (clinicaltrials.gov/ct2/show/NCT00130299) Primary outcome measure(s): adiposity Secondary outcome measure(s): HLD, LDL, triglyceride, blood pressure, plasma glucose level, and serum insulin Other outcome measure(s): not available Trial results available in trial register: yes  Endpoints quoted in publications Primary outcome measure(s): body weight, body fat percentage Secondary outcome measure(s): HLD, LDL, triglyceride, blood pressure, plasma glucose level, serum insulin, adverse event, dietary adherence Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight, body fat percentage Secondary outcome measure(s): insulin concentration, HDL, LDL Other outcome measures: not available Comments: the study protocol was available and all the study's prespecified outcomes that were of interest to this review were reported in the prespecified way.
Other bias	Low risk	Comment: no other potential sources of bias detected.

Gardner 2018.

Study characteristics
Methods	Study design: parallel randomised controlled trial Number of study centres: 1
Participants	Inclusion criteria: men and premenopausal women, 18 to 50 years old, BMI between 28 to 40 kg/m2 Exclusion criteria: uncontrolled hypertension or metabolic disease, diabetes, cancer, heart disease, renal disease, liver disease, pregnant, lactating, taking medication; hypoglycaemic, lipid‐lowering, antihypertensive, psychiatric, or other medications affecting body weight or energy expenditure Diagnostic criteria: NR Setting: community setting/free‐living individuals Age group: adults  Gender distribution: females and males Country/countries where study was performed: USA
Interventions	Intervention(s): low‐carbohydrate diet  “Go as low as you can go” (Limbo) strategy for the first eight weeks until participants achieve a daily intake of no more than 20 grams of carbohydrates per day Once participants reached their lowest level of carbohydrates intake, they were encouraged to maintain that level for at least a few weeks Participants were then encouraged to shift their daily goal to 25 to 35 grams/day for a week or for possibly more than one week Participants had the option of maintaining that level of  carbohydrates intake for another week or adding an incremental 5 to 15 grams/day based on their satisfaction with their daily intake and their weight loss progress Participants then could either reduce, maintain, or increase their carbohydrates intake for the remainder of the study. Comparator(s): low‐fat diet “Go as low as you can go” (Limbo) strategy for the first eight weeks until participants achieve a daily intake of no more than 20 grams of fats per day Once participants reached their lowest level of fats intake, they were encouraged to maintain that level for at least a few weeks Participants were then encouraged to shift their daily goal to 25 to 35 grams/day for a week or for possibly more than one week Participants had the option of maintaining that level of fats intake for another week or adding an incremental 5 to 15 grams/day based on their satisfaction with their daily intake and their weight loss progress Participants then could either reduce, maintain, or increase their fats intake for the remainder of the study TIDieR description of the intervention: Brief name: low‐fat versus low‐carbohdyrate diet on 12 months weight loss in overweight adults Recipient: "We aimed to recruit 600 adults from the Stanford and San Francisco Bay areas of California using media advertisements and email lists from previous recruitment for nutrition studies conducted by our laboratory group... We considered men and premenopausal women aged 18 to 50 years with a BMI of 28 to 40."  Why: "Among many strategies studied for weight loss, a common contrast has been low‐fat diets vs low‐carbohydrate diets. Most diet trials have reported modest (ie, < 5%) mean weight loss after 12 months and negligible mean weight loss differences between diet groups. In contrast, individual weight losses have varied widely within diet groups in these studies, ranging from approximately 25 kg lost to approximately 5 kg gained. The substantial variability of weight loss response suggests some strategies may work better for some individuals than others, and that no one diet should be recommended universally. Yet, interindividual differences in response to diet are poorly understood. Some studies have reported that genotype variation could predispose individuals to differential weight loss that varies by diet type." What (materials): "participants were instructed to reduce intake of total fat or digestible carbohydrates to 20 g/d during the first 8 weeks... Then individuals slowly added fats or carbohydrates back to their diets in increments of 5 to 15 g/d per week until they reached the lowest level of intake they believed could be maintained indefinitely. No explicit instructions for energy (kilocalories) restriction were given." What (procedures): "The intervention involved 22 instructional sessions held over 12 months in diet‐specific groups of approximately 17 participants per class. Sessions were held weekly for 8 weeks, then every 2 weeks for 2 months, then every 3 weeks until the sixth month, and monthly thereafter." Who provided: "Classes were led by 5 registered dietitian health educators who each taught 1 healthy low‐fat class and 1 healthy low‐carbohydrate class per cohort. Dietitians were blinded to all laboratory measures and genotype" How (mode of delivery; individual or group): "The intervention involved a series of 22 evening instructional sessions in groups of 12‐22 participants per class. Participants attended classes with the same group of individuals over time." The classes were conducted face to face.  Where: intervention classes were conducted in a large meeting room at the medical school research building that houses the research team (1070 Arastradero, Palo Alto, CA) When and how much: the intervention involved 22 instructional sessions held over 12 months in diet‐specific groups of approximately 17 participants per class. Sessions were held weekly for 8 weeks, then every 2 weeks for 2 months, then every 3 weeks until the sixth month, and monthly thereafter. Tailoring: NR Modification of intervention throughout the study: "When this study was first designed, insulin sensitivity was to be measured and used as a predictor of differential weight loss success. After the study was initiated, reports were published indicating INS‐30 [blood concentration of insulin 30 minutes after a glucose challenge] was a successful predictor of weight loss in the context of low‐carbohydrate diets or similar diets. There also was evidence that early‐phase insulin secretion differed markedly between diets that were similar to those tested in the DIETFITS study. Prior to examining any data, we modified the primary hypothesis of our study and tested baseline INS‐30 rather than a measure of insulin sensitivity as the putative effect modifier. No other glucose or insulin variables were tested for effect modification." Strategies to improve or maintain intervention fidelity: NR Extent of intervention fidelity: "Dietary intake of fats and carbohydrates was well differentiated between the 2 diet groups, as confirmed by diet assessment, and corroborated by changes in blood lipid parameters and respiratory exchange ratio, indicating strong treatment fidelity." Duration of intervention: 52 weeks Duration of follow‐up: NR Run‐in period: 4 weeks
Outcomes	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: NCT01826591 (clinicaltrials.gov/ct2/show/NCT01826591) Primary outcome measure(s): bodyweight Secondary outcome measure(s): BMI, body fat, LDL, HDL, triglyceride, fasting insulin, fasting glucose, adverse events  Other outcome measure(s): not available Trial results available in trial register: no Endpoints quoted in publications Primary outcome measure(s): bodyweight Secondary outcome measure(s): BMI, body fat, wasit circumference, HDL, LDL, triglyceride, systolic blood pressure, diastolic blood pressure, fasting insulin, fasting glucose, dietary adherence  Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight Secondary outcome measure(s): not available Other outcome measures: not available
Study registration	Trial identifier: NCT01826591 Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English Funding: non‐commercial funding: 1)  The National Institute of Diabetes and Digestive and Kidney Diseases (grant 1R01DK091831); 2) The Nutrition Science Initiative (grants 1K12GM088033); 3) The National Heart, Lung, and Blood Institute; 4) The Stanford Clinical and Translational Science Award Declaration of interest: none to declare Publication status: peer‐reviewed journal
Stated aim of study	Quote: "To determine the effect of a healthy low‐fat (HLF) diet vs a healthy low‐carbohydrate (HLC) diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss."
Notes	Contact with study authors: 23 April 2021 for information about (1) venue where intervention classes conducted; (2) adverse events and serious adverse events. Response: 2 May 2021: (1) venue of the intervention classes was provided; (2) author was unable to provide any further information on the adverse events and serious adverse events.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization to a healthy low‐fat diet or a healthy low‐carbohydrate diet was performed using an allocation sequence determined by computerized random‐number generation (Blockrand in R version 3.4.0; R Project for Statistical Computing) in block sizes of 8 (with 4 individuals going to each diet) by a statistician not involved in intervention delivery or data collection." Comment: study authors achieved sequence generation using computer‐generated random numbers.
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information about allocation concealment.
Blinding of participants and personnel (performance bias) Anthropometric measures	Unclear risk	Quote: "The study was single‐blinded. It was not feasible to blind participants to Healthy Low‐Fat vs. Healthy Low‐Carb dietary assignment. However, for all staff collecting data (e.g., dietary assessment, DXA) and for all laboratory personnel assaying samples (e.g., insulin, glucose), diet group assignments were masked" Comment: only blinding of study personnel was possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Adverse events	Unclear risk	Quote: "The study was single‐blinded. It was not feasible to blind participants to Healthy Low‐Fat vs. Healthy Low‐Carb dietary assignment. However, for all staff collecting data (e.g., dietary assessment, DXA) and for all laboratory personnel assaying samples (e.g., insulin, glucose), diet group assignments were masked" Comment: only blinding of study personnel was possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Glycaemic control	Unclear risk	Quote: "The study was single‐blinded. It was not feasible to blind participants to Healthy Low‐Fat vs. Healthy Low‐Carb dietary assignment. However, for all staff collecting data (e.g., dietary assessment, DXA) and for all laboratory personnel assaying samples (e.g., insulin, glucose), diet group assignments were masked" Comment: only blinding of study personnel was possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Insulin action	Unclear risk	Quote: "The study was single‐blinded. It was not feasible to blind participants to Healthy Low‐Fat vs. Healthy Low‐Carb dietary assignment. However, for all staff collecting data (e.g., dietary assessment, DXA) and for all laboratory personnel assaying samples (e.g., insulin, glucose), diet group assignments were masked" Comment: only blinding of study personnel was possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Cardiovascular risk factors	Unclear risk	Quote: "The study was single‐blinded. It was not feasible to blind participants to Healthy Low‐Fat vs. Healthy Low‐Carb dietary assignment. However, for all staff collecting data (e.g., dietary assessment, DXA) and for all laboratory personnel assaying samples (e.g., insulin, glucose), diet group assignments were masked" Comment: only blinding of study personnel was possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Dietary adherence	Unclear risk	Quote: "The study was single‐blinded. It was not feasible to blind participants to Healthy Low‐Fat vs. Healthy Low‐Carb dietary assignment. However, for all staff collecting data (e.g., dietary assessment, DXA) and for all laboratory personnel assaying samples (e.g., insulin, glucose), diet group assignments were masked" Comment: only blinding of study personnel was possible due to the nature of the study.
Blinding of outcome assessment (detection bias) Anthropometric measures	Low risk	Quote: "Staff who measured outcomes were blinded to diet assignment, genotype pattern, and INS‐30 [blood concentration of insulin 30 minutes after a glucose challenge]." Comment: blinding of outcome assessment is ensured.
Blinding of outcome assessment (detection bias) Glycaemic control	Low risk	Quote: "Staff who measured outcomes were blinded to diet assignment, genotype pattern, and INS‐30." Comment: blinding of outcome assessment is ensured.
Blinding of outcome assessment (detection bias) Insulin action	Low risk	Quote: "Staff who measured outcomes were blinded to diet assignment, genotype pattern, and INS‐30." Comment: blinding of outcome assessment is ensured.
Blinding of outcome assessment (detection bias) Cardiovascular risk factors	Low risk	Quote: "Staff who measured outcomes were blinded to diet assignment, genotype pattern, and INS‐30." Comment: blinding of outcome assessment is ensured.
Blinding of outcome assessment (detection bias) Adverse events	Unclear risk	Comment: insufficient information; it was not clear whether outcome was self‐reported or investigator‐assessed.
Blinding of outcome assessment (detection bias) Dietary adherence	High risk	Quote: "Dietary intake at each time point was assessed using 3 unannounced 24‐hour multiple‐pass recall interviews (2 on weekdays and 1 on a weekend day)." Comment: self‐reporting was part of the 24‐hour multiple pass recall interviews.
Incomplete outcome data (attrition bias) Anthropometric measures	Low risk	Quote: "We applied modified intent‐to‐treat principles." Comment: attrition rate was similar between arms (healthy low‐fat diet: 20.9%, healthy low‐carbohydrate diet: 21.7%). Imputation was used to handle missing data.
Incomplete outcome data (attrition bias) Glycaemic control	Low risk	Quote: "We applied modified intent‐to‐treat principles." Comment: attrition rate was similar between arms (healty low‐fat diet;20.9%, healthy low‐carbohdyrate diet; 21.7%). Imputation was used to handle missing data.
Incomplete outcome data (attrition bias) Insulin action	Low risk	Quote: "We applied modified intent‐to‐treat principles." Comment: attrition rate was similar between arms (healty low‐fat diet;20.9%, healthy low‐carbohdyrate diet; 21.7%). Imputation was used to handle missing data.
Incomplete outcome data (attrition bias) Cardiovascular risk factors	Low risk	Quote: "We applied modified intent‐to‐treat principles." Comment: attrition rate was similar between arms (healty low‐fat diet;20.9%, healthy low‐carbohdyrate diet; 21.7%). Imputation was used to handle missing data.
Incomplete outcome data (attrition bias) Adverse events	Unclear risk	Comment: insufficient information
Incomplete outcome data (attrition bias) Dietary adherence	High risk	Comment: at baseline, dietary intake of 304 participants from each group was analysed. At 12 months, only 224 and 225 participants from the intervention group and control groups, respectively, were analysed.
Selective reporting (reporting bias)	Low risk	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: NCT01826591 (clinicaltrials.gov/ct2/show/NCT01826591) Primary outcome measure(s): bodyweight Secondary outcome measure(s): BMI, body fat, LDL, HDL, triglyceride, fasting insulin, fasting glucose, adverse event  Other outcome measure(s): not available Trial results available in trial register: no Endpoints quoted in publications Primary outcome measure(s): bodyweight Secondary outcome measure(s): BMI, body fat, wasit circumference, HDL, LDL, triglyceride, systolic blood pressure, diastolic blood pressure, fasting insulin, fasting glucose, dietary adherence  Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight Secondary outcome measure(s): not available Other outcome measures: not available Comment: the study protocol was available and all the study's prespecified outcomes that were of interest to this review were reported in the prespecified way.
Other bias	Low risk	Comment: no other potential sources of bias detected.

Goss 2013.

Study characteristics
Methods	Study design: parallel randomised controlled trial Number of study centres: 1
Participants	Inclusion criteria: healthy overweight or obese (BMI > 25) African American and European Americans, aged 21 to 50 years, females were all premenopausal, sedentary (< 2 hours/week activity), non‐diabetic, non‐smokers, and weight stable for 6 months prior to enroling in the study Exclusion criteria: NR Diagnostic criteria: NR Setting: community setting/free‐living individuals Age group: adults Gender distribution: females and males Country/countries where study was performed: USA
Interventions	Intervention(s): low GL diet  Low GL diet (≤ 45 points per 1000 kcal; 43% carbohydrate, 18% protein, 39% fat) The average GI of the foods included on the low GL diet was 49 points Comparator(s): high GL diet High GL diet (≥ 75 points per 1000 kcal, 59% carbohydrate, 18% protein, 27% fat) The average GI of the foods included on the high GL diet was 60 points TIDieR description of the intervention: Brief name: low GL diet versus high GL diet for overweight or obese individuals  Recipient: "Healthy overweight or obese (BMI>25) African American and European Americans (52% European American; 45% male), aged 21–50 years" Why: "Hypothesize that consumption of a relatively low glycemic load (GL) diet would reduce total and visceral adipose tissue under both eucaloric and hypocaloric conditions" What (materials): "Intervention diet menus were designed using Nutrition Data System for Research (NDSR) software versions 2006 and 2007 (Nutrition Coordinating Center (NCC), University of Minnesota, Minneapolis, MN). All food was provided by the General Clinical Research Unit (GCRC) Metabolic Kitchen." What (procedures): "Participants completed a 4 day food record (3 week days, 1 weekend day) for assessment of typical, free‐living, nutrient intake prior to beginning the 16‐wk dietary intervention. After completing the food record, all subjects consumed the same diet for habituation (3 days). The dietary intervention included 2 phases: 8‐wks under eucaloric conditions followed by 8‐wks under hypocaloric conditions. Dual‐energy X‐ray absorptiometry (DXA) and computed tomography (CT) scans were acquired for all participants at baseline, following the 8‐wk eucaloric phase, and following the subsequent 8‐wk hypocaloric phase." Who provided: "All food was provided by the General Clinical Research Unit (GCRC) Metabolic Kitchen" How (mode of delivery; individual or group): "For the duration of the intervention, participants reported to the General Clinical Research Center each weekday morning to be weighed, eat breakfast, and collect food for their remaining meals. On Fridays, participants picked up food for Saturday and Sunday to consume at home." Where: "For the duration of the intervention, participants reported to the General Clinical Research Center each weekday morning to be weighed, eat breakfast, and collect food for their remaining meals. On Fridays, participants picked up food for Saturday and Sun" When and how much: "Participants completed a 4 day food record (3 week days, 1 weekend day) for assessment of typical, free‐living, nutrient intake. After completing the food record, all subjects consumed the same diet for habituation (3 days). The dietary intervention included 2 phases: 8‐wks under eucaloric conditions followed by 8‐wks under hypocaloric conditions." Tailoring: NR Modification of intervention throughout the study: NR Strategies to improve or maintain intervention fidelity: NR Extent of intervention fidelity: NR Duration of intervention: 16 weeks Duration of follow‐up: NR Run‐in period: NR
Outcomes	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper)  Source: NCT00726908 (clinicaltrials.gov/ct2/show/NCT00726908) Primary outcome measure(s): insulin sensitivity  Secondary outcome measure(s): body weight Other outcome measure(s): not available Trial results available in trial register: No Endpoints quoted in publications Primary outcome measure(s): weight, total lean, total fat Secondary outcome measure(s): not available Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight, total fat Secondary outcome measure(s): not available Other outcome measures: not available
Study registration	Trial identifier: NR Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English Funding: other funding: (R01DK67538, M01‐RR‐00032, UL1RR025777, P30‐DK56336, P60DK079626) Declaration of interest: none to declare Publication status: peer‐reviewed journal
Stated aim of study	Quote: "The objective of this study was to test the hypothesis that consumption of a relatively low GL diet would reduce total and regional adipose tissue during both weight maintenance and weight loss conditions. A secondary aim was to determine if there is a sexual dimorphism in outcomes of interest"
Notes	Contact with study authors: on 26 April 2021 and 4 June 2021 to request information about: (1) number of individuals screened, eligible, randomised, analysed for primary outcome, and completed the study; (2) description of sample size calculation; (3) strategies to improve or maintain intervention fidelity; (4) outcome reported as mean change (kg) ± SD. Response on 4 June 2021: all requested information was provided.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: randomisation method was not described
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information about the allocation concealment
Blinding of participants and personnel (performance bias) Anthropometric measures	Unclear risk	Quote: "Participants were blinded to an assigned diet which was either the low GL diet or the high GL diet" Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of outcome assessment (detection bias) Anthropometric measures	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Incomplete outcome data (attrition bias) Anthropometric measures	Unclear risk	Comment: attrition was greater in the low GL group (low GL: n = 9; high GL: n = 1). Reasons for attrition were not clearly stated.
Selective reporting (reporting bias)	Unclear risk	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper)  Source: NCT00726908 (clinicaltrials.gov/ct2/show/NCT00726908) Primary outcome measure(s): insulin sensitivity  Secondary outcome measure(s): body weight Other outcome measure(s): not available Trial results available in trial register: no Endpoints quoted in publications Primary outcome measure(s): weight, total lean, total fat Secondary outcome measure(s): not available Other outcome measures: not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight, total fat Secondary outcome measure(s): not available Other outcome measures: not available Comment: insufficient information to assess risk of selective reporting
Other bias	Low risk	Comment: no other potential sources of bias detected.

McMillan‐Price 2006.

Study characteristics
Methods	Study design: parallel randomised controlled trial Number of study centres: 1
Participants	Inclusion criteria: 18 to 40 years old, BMI ≥ 28 kg/m2, body weight < 150 kg, weight fluctuations < 5 kg in the last 2 months, willing to eat red meat and maintain current physical activity Exclusion criteria: chronic illness, regular medication other than birth control pills, eating disorders, special diets, pregnancy, food allergy, and insufficient command of English language Diagnostic criteria: NR Setting: community setting/free‐living individuals Age group: young adults Gender distribution: females and males Country/countries where study was performed: Australia
Interventions	Intervention(s):  High carbohydrate, low GI diet High carbohydrate (55% of energy) and average protein (15% of energy) diet based on verified low GI foods Reduced‐energy, reduced‐fat (30% of energy), moderate‐fiber (30 g/day) High protein, low GI diet High protein (25% of energy) and carbohydrate‐reduced (45% of energy) diet based on lean red meat and verified low GI foods Reduced‐energy, reduced‐fat (30% of energy), moderate‐fiber (30 g/day) Comparator(s):  High carbohydrate, high GI diet High carbohydrate (55% of energy) and average protein (15% of energy) diet based on high GI whole grains, including fiber‐rich breakfast cereals and bread Reduced‐energy, reduced‐fat (30% of energy), moderate‐fiber (30 g/day) High protein, high GI diet High protein (25% of energy) and carbohydrate reduced (45% of energy) diet based on lean red meat and high GI whole grains Reduced‐energy, reduced‐fat (30% of energy), moderate‐fiber (30 g/day) TIDieR description of the intervention: Brief name: comparison pair 1: comparison of high carbohdyrate diet with either low GI or high GI foods on weight loss and cardiovascular risk reduction in overweight and obese young adults. Comparison pair 2: comparison of high protein diet with either low GI or high GI foods on weight loss and cardiovascular risk reduction in overweight and obese young adults Recipient: overweight (≥ 25 kg/m2), young adults (18 to 40 years old) were recruited locally using notice boards and news paper advertisements.  Why: "Both low–glycemic index (GI) and high‐protein diets have caught the public’s attention, but clinicians and health professionals remain skeptical, calling for greater scientific evidence on which to base advice to patients. One concern is that many sources of protein, such as meat and dairy products, can also be high in saturated fat. The accelerating obesity epidemic, the widespread popularity of alternate diets, and animal studies showing ß‐cell disruption on high‐GI diets make the need for resolution of the debate more pressing." What (materials): "Subjects were given eating plans that were devised to help them lose weight (providing approximately 1400 kcal [6000 kJ] for women and 1900 kcal [8000 kJ] for men) and achieve the desired macronutrient distribution. These plans specified the number of servings from each food group and suitable choices within each group. Additional lists of appropriate meals and snacks were also provided. Dairy intake was held constant to minimize confounding from this source. To allow satiety and appetite factors to function, subjects were told to “eat to appetite” but were not required to consume all specified servings and, if hungry, were permitted to increase the number of servings proportionately from each food group." What (procedures): "To maximize compliance, all key CHO [carbohydrate] and protein foods and some preprepared meals were provided. A color‐coded “shop” system (different color for each diet) with bar code reader was used, and subjects collected foods of low or high GI (eg, bread, breakfast cereal, crackers, snack bars, oats, legumes, pasta, and basmati or jasmine rice), red meat portions, and specially prepared frozen meals each week. On the same day, they met with a dietitian who encouraged compliance and answered queries." Who provided: participants met with a dietitian who encouraged compliance and answered queries. How (mode of delivery; individual or group): face to face. Not reported whether it was individual or in group. Where: "Volunteers were recruited locally using notice boards and newspaper advertisements." No other description provided. When and how much: NR Tailoring: "Participants were given eating plans providing 1400kcal for women and 1900kcal for men to achieve weight loss and achieve macronutrients distribution." Modification of intervention throughout the study: NR Strategies to improve or maintain intervention fidelity: "To maximize compliance, all key CHO [carbohdyrate] and protein foods and some preprepared meals were provided. A color‐coded “shop” system (different color for each diet) with bar code reader was used, and subjects collected foods of low or high GI (eg, bread, breakfast cereal, crackers, snack bars, oats, legumes, pasta, and basmati or jasmine rice), red meat portions, and specially prepared frozen meals each week." On the same day, they met with a dietitian who encouraged compliance and answered queries. Extent of intervention fidelity: at baseline and during weeks 4 and 8, subjects were asked to keep a 3‐day food diary, including 2 weekdays and 1 weekend day, to assess dietary compliance and to estimate food intake. Duration of intervention: 12 weeks Duration of follow‐up: NR Run‐in period: NR
Outcomes	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper)  Source: NCT00254215 (clinicaltrials.gov/ct2/show/NCT00254215) Primary outcome measure(s): weight loss, fat loss, lean mass change Secondary outcome measure(s): total cholesterol, HDL, LDL, triglycerol, glucose, insulin, insulin sensitivity, dietary adherence  Other outcome measure(s): not available Trial results available in trial register: no Endpoints quoted in publications Primary outcome measure(s): weight loss, waist change, fat loss, lean mass change Secondary outcome measure(s): total cholesterol, HDL, LDL, triglycerol, glucose, insulin, insulin sensitivity, dietary adherence  Other outcome measure(s): not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): weight loss, fat loss Secondary outcome measure(s): LDL Other outcome measures: not available
Study registration	Trial identifier: NCT00254215 Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English  Funding: non‐commercial funding: National Heart Foundation and Meat and Livestock Australia Declarations of interest: quote: "Ms McMillan‐Price and Dr Brand‐Miller are coauthors of The Low GI Diet Revolution (Marlowe & Co., New York, NY 2005). Dr Brand‐Miller is a coauthor of The New Glucose Revolution book series (Hodder and Stoughton, London, England; Marlowe & Co; and Hodder Headline, Sydney, and elsewhere)". Publication status: peer‐reviewed journal
Stated aim of study	Quote: "More recently there has been interest in low glycemic index and high protein diets with some evidence that these produce better fat loss and improvement in cardiovascular risk factors. This trial aims to evaluate these different approaches and compare the outcomes over 12 weeks."
Notes	Contact with study authors: on 24 April 2021. No reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "subjects were stratified according to weight (<80 kg, 80‐100 kg, and >100 kg) and sex and then randomly assigned to 1 of the 4 diets, which resulted in 4 well‐matched groups with no significant differences in baseline characteristics" Comment: randomisation method not stated. However, groups appear to have similar baseline characteristics.
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information about allocation concealment
Blinding of participants and personnel (performance bias) Anthropometric measures	Unclear risk	Comment: insufficient information about blinding of participants and study personnel
Blinding of participants and personnel (performance bias) Glycaemic control	Unclear risk	Comment: insufficient information about blinding of participants and study personnel
Blinding of participants and personnel (performance bias) Insulin action	Unclear risk	Comment: insufficient information about blinding of participants and study personnel
Blinding of participants and personnel (performance bias) Cardiovascular risk factors	Unclear risk	Comment: insufficient information about blinding of participants and study personnel
Blinding of participants and personnel (performance bias) Dietary adherence	Unclear risk	Comment: insufficient information about blinding of participants and study personnel
Blinding of outcome assessment (detection bias) Anthropometric measures	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Glycaemic control	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Insulin action	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Cardiovascular risk factors	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Dietary adherence	High risk	Quote: "At baseline and during weeks 4 and 8, subjects were asked to keep a 3‐day food diary, including 2 weekdays and 1 weekend day, to assess dietary compliance and to estimate food intake." Comment: self‐reported dietary intake
Incomplete outcome data (attrition bias) Anthropometric measures	Low risk	Quote: "Missing data were replaced with the last known value for the primary intention‐to‐treat analysis and excluded in the secondary analysis... Of the 129 enrolled subjects, 13 dropped out (all female): 1 became pregnant, 1 failed to complete the final analysis, 2 moved interstate, and 9 cited disappointment with the rate of weight loss." Comments: although reasons for discontinuation were reported overall and not specified by intervention arms, intention‐to‐treat analysis was employed.
Incomplete outcome data (attrition bias) Glycaemic control	Low risk	Quote: "Missing data were replaced with the last known value for the primary intention‐to‐treat analysis and excluded in the secondary analysis... Of the 129 enrolled subjects, 13 dropped out (all female): 1 became pregnant, 1 failed to complete the final analysis, 2 moved interstate, and 9 cited disappointment with the rate of weight loss." Comments: although reasons for discontinuation were reported overall and not specified by intervention arms, intention‐to‐treat analysis was employed.
Incomplete outcome data (attrition bias) Insulin action	Low risk	Quote: "Missing data were replaced with the last known value for the primary intention‐to‐treat analysis and excluded in the secondary analysis... Of the 129 enrolled subjects, 13 dropped out (all female): 1 became pregnant, 1 failed to complete the final analysis, 2 moved interstate, and 9 cited disappointment with the rate of weight loss." Comments: although reasons for discontinuation were reported overall and not specified by intervention arms, intention‐to‐treat analysis was employed.
Incomplete outcome data (attrition bias) Cardiovascular risk factors	Low risk	Quote: "Missing data were replaced with the last known value for the primary intention‐to‐treat analysis and excluded in the secondary analysis... Of the 129 enrolled subjects, 13 dropped out (all female): 1 became pregnant, 1 failed to complete the final analysis, 2 moved interstate, and 9 cited disappointment with the rate of weight loss." Comments: although reasons for discontinuation were reported overall and not specified by intervention arms, intention‐to‐treat analysis was employed.
Incomplete outcome data (attrition bias) Dietary adherence	Low risk	Quote: "Missing data were replaced with the last known value for the primary intention‐to‐treat analysis and excluded in the secondary analysis... Of the 129 enrolled subjects, 13 dropped out (all female): 1 became pregnant, 1 failed to complete the final analysis, 2 moved interstate, and 9 cited disappointment with the rate of weight loss." Comments: although reasons for discontinuation were reported overall and not specified by intervention arms, intention‐to‐treat analysis was employed.
Selective reporting (reporting bias)	Low risk	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper)  Source: NCT00254215 (clinicaltrials.gov/ct2/show/NCT00254215) Primary outcome measure(s): weight loss, fat loss, lean mass change Secondary outcome measure(s): total cholesterol, HDL, LDL, triglycerol, glucose, insulin, insulin sensitivity, dietary adherence  Other outcome measure(s): not available Trial results available in trial register: No Endpoints quoted in publications Primary outcome measure(s): weight loss, waist change, fat loss, lean mass change Secondary outcome measure(s): total cholesterol, HDL, LDL, triglycerol, glucose, insulin, insulin sensitivity, dietary adherence  Other outcome measure(s): not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): weight loss, fat loss Secondary outcome measure(s): LDL Other outcome measures: not available Comments: the study protocol was available and all the study's prespecified outcomes that were of interest to this review were reported in the prespecified way.
Other bias	Low risk	Comment: no other potential sources of bias detected.

Rouhani 2013.

Study characteristics
Methods	Study design: parallel randomised controlled trial Number of study centres: 1
Participants	Inclusion criteria: healthy overweight/obese girls at pubertal ages, being female, < 18 years old, overweight or obese, menstruating and not using medications Exclusion criteria: low adherence to recommendations, use medications which may influence appetite and weight Diagnostic criteria: NR Setting: community setting/free‐living individuals Age group: adolescents Gender distribution: females  Country/countries where study was performed: Iran
Interventions	Intervention(s): low glycemic index (LGI) diet TEE was restricted by 200 kilocalorie for those in > 95th percentile of BMI for age according to the WHO table 53% to 56% of total calorie from carbohydrates, 16% to 18% from proteins, and 27% to 30% from fats Participants were recommended to consume foods with GI < 50 and were forbidden to consume high GI foods Comparator(s): healthy nutritional recommendations‐ (HNR) based diet TEE was restricted by 200 kilocalorie for those in > 95th percentile of BMI for age according to WHO table 53% to 56% of total calorie from carbohydrates, 16% to 18% from proteins, and 27% to 30% from fats May cover low GI‐based recommendations; to consume whole grains. However, these two kinds of recommendations are different in the fruit and vegetable food groups TIDieR description of the intervention: Brief name: low GI or a healthy nutritional recommendations‐ (HNR) based diet for healthy overweight/obese girls at pubertal ages Recipient: healthy overweight/obese girls at pubertal ages Why: "There is little evidence regarding the effect of an LGI diet on lipid profiles, especially apolipoproteins and lipoprotein (a) (Lpa) among children and adolescents" What (materials): "Low glycemic index (LGI) or a healthy nutritional recommendations (HNR) based diet with similar macronutrient composition (53–56 % en carbohydrate, 16–18 % en protein, and 27–30 % en fat) was prescribed for both groups." What (procedures): "Volunteers completed a 1‐day weighed dietary record and a 1‐day physical activity record in weeks 2.5, 5, 7.5 and 10 of the study. The participants completed a 4‐day food record and a 4‐day physical activity record to include 1 weekend and 3 week days. In individual sessions, records were evaluated and clarified. At each visit, one dietitian answered participants’ queries. For assessing biochemical variables, one blood sample was drew [sic] after 12 h overnight fasting from each participant at baseline and at the end of week 10."  Who provided: "Dietary interventions were comprehensively explained to the adolescents and their parents. All the meals were provided by parents" How (mode of delivery; individual or group): "In the intervention group, adolescents were directed to select carbohydrate containing foods included fruits, vegetables, dairy and grains from a list of LGI foods. Furthermore, they were advised to curtail the intake of high glycemic index (HGI) foods (GI > 50). Regarding food choices of meat and fat, adolescents were given a standard food exchange list. Individual sessions were established for teaching the prescribed diet. The participants in the HNR group were given food lists emphasizing the limitation of unhealthy food such as fast foods, french fries, fried foods, industrial beverages and unhealthy fats, they were advised to drink 1.5–2 l of water, consume a large amount of fruit and vegetables of different varieties, low fat dairy and whole grains. HNR group is provided with a complete food exchange list for selecting the foods."  Where: "This study was conducted in Isfahan, Iran in 2011" When and how much: "Volunteers completed a 1‐day weighed dietary record and a 1‐day physical activity record in weeks 2.5, 5, 7.5 and 10 of the study. The participants completed a 4‐day food record and a 4‐day physical activity record to include 1 weekend and 3 week days. For dietary intervention, adolescents were randomized to either an LGI or an HNR‐based diet for a 10‐week period. For biochemical variables, one blood sample was drew [sic] after 12 h overnight fasting from each participant at baseline and at the end of week 10." Tailoring: NR Modification of intervention throughout the study: NR Strategies to improve or maintain intervention fidelity: NR Extent of intervention fidelity: NR Duration of intervention: 10 weeks Duration of follow‐up: NR Run‐in period: NR
Outcomes	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper):  Source: IRCT201109272839N4 (en.irct.ir/trial/2696) Primary outcome measure(s): dietary record, body weight Secondary outcome measure(s): BMI, height, waist circumference, systolic blood pressure, diastolic blood pressure, HDL, LDL, fasting blood glucose, total cholesterol, tryglyceride, insulin  Other outcome measure(s): not available Trial results available in trial register: no Endpoints quoted in publications Primary outcome measure(s): weight Secondary outcome measure(s): waist circumference, BMI, systolic blood pressure, diastolic blood pressure, triacylglycerol, total cholesterol, HDL, LDL, fasting blood sugar (FBS), serum insulin concentration, homeostasis model assessment (HOMA), dietary adherence  Other outcome measure(s): not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): blood pressure, weight and waist circumference, lipid profile  Secondary outcome measure(s): not available Other outcome measures: not available
Study registration	Trial identifier: IRCT201109272839N4 Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English  Funding: other funding: a grant from the Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran Declaration of interest: none to declare Publication status: peer‐reviewed journal
Stated aim of study	Quote: "we aimed to determine the medium term effects of LGI diet in comparison to the HNR on obesity and blood pressure among adolescent girls in pubertal ages"
Notes	Contact with study authors: attempted on 26 April 2021. No reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Adolescents were randomized to either an LGI (n = 25) or an HNR‐based diet (n = 25) for a 10‐week period" Comment: randomisation method not stated. However, groups appear to have similar baseline characteristics.
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information about allocation concealment
Blinding of participants and personnel (performance bias) Anthropometric measures	Unclear risk	Quote: "Adolescents were not blinded to the kind of diet that they consumed. Weight was measured during each visit by a blinded assistance" Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Glycaemic control	Unclear risk	Quote: "Adolescents were not blinded to the kind of diet that they consumed. Weight was measured during each visit by a blinded assistance" Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Insulin action	Unclear risk	Quote: "Adolescents were not blinded to the kind of diet that they consumed. Weight was measured during each visit by a blinded assistance" Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Cardiovascular risk factors	Unclear risk	Quote: "Adolescents were not blinded to the kind of diet that they consumed. Weight was measured during each visit by a blinded assistance" Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Dietary adherence	Unclear risk	Quote: "Adolescents were not blinded to the kind of diet that they consumed. Weight was measured during each visit by a blinded assistance" Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of outcome assessment (detection bias) Anthropometric measures	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Glycaemic control	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Insulin action	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Cardiovascular risk factors	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Dietary adherence	High risk	Quote: "The participants completed a 4‐day food record and a 4‐day physical activity record to include 1 weekend and 3 week days." Comment: self‐reported dietary intake
Incomplete outcome data (attrition bias) Anthropometric measures	High risk	Comment: appropriate methods, such as multiple imputation, were not used to handle missing data as results were only reported for completers.
Incomplete outcome data (attrition bias) Glycaemic control	High risk	Comment: appropriate methods, such as multiple imputation, were not used to handle missing data as results were only reported for completers.
Incomplete outcome data (attrition bias) Insulin action	High risk	Comment: appropriate methods, such as multiple imputation, were not used to handle missing data as results were only reported for completers.
Incomplete outcome data (attrition bias) Cardiovascular risk factors	High risk	Comment: appropriate methods, such as multiple imputation, were not used to handle missing data as results were only reported for completers.
Incomplete outcome data (attrition bias) Dietary adherence	High risk	Comment: appropriate methods, such as multiple imputation, were not used to handle missing data as results were only reported for completers.
Selective reporting (reporting bias)	Low risk	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper):  Source: IRCT201109272839N4 (en.irct.ir/trial/2696) Primary outcome measure(s): dietary record, body weight Secondary outcome measure(s): BMI, height, waist circumference, systolic blood pressure, diastolic blood pressure, HDL, LDL, fasting blood glucose, total cholesterol, tryglyceride, insulin  Other outcome measure(s): not available Trial results available in trial register: no Endpoints quoted in publications Primary outcome measure(s): weight Secondary outcome measure(s): waist circumference, BMI, systolic blood pressure, diastolic blood pressure, triacylglycerol, total cholesterol, HDL, LDL, fasting blood sugar (FBS), serum insulin concentration, homeostasis model assessment (HOMA), dietary adherence  Other outcome measure(s): not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): blood pressure, weight and waist circumference, lipid profile  Secondary outcome measure(s): not available Other outcome measures: not available Comment: the study protocol was available and all the study's prespecified outcomes that were of interest to this review were reported in the prespecified way.
Other bias	Low risk	Comment: no other potential sources of bias detected.

Solomon 2010.

Study characteristics
Methods	Study design: parallel randomised controlled trial Number of study centres: 1
Participants	Inclusion criteria: obese patients with prediabetes [age 66 ± 1 year], BMI: 34.4 ± 2.8 kg/m2, weight stable for previous 6 months Exclusion criteria: medical screenings excluded individuals with heart, kidney, liver, thyroid, intestinal, and pulmonary diseases or individuals taking medications known to affect the outcome variables of the study. Postmenopausal using hormone replacement therapy. Low adherence to recommendations Diagnostic criteria: medical screening; resting 12‐lead electrocardiograms and submaximal exercise stress test Setting: community setting/free‐living individuals Age group: adults Gender distribution: females and males Country/countries where study was performed: USA
Interventions	Intervention(s): low GI diet plus exercise GI of diet is 40 arbitrary units  60 minutes aerobic exercise (treadmill walking and cycle ergometry at 85% maximum heart rate) 5 days/week for 12 weeks Comparator(s): high GI diet plus exercise GI of diet is 80 arbitrary units 60 minutes aerobic exercise (treadmill walking and cycle ergometry at 85% maximum heart rate) 5 days/week for 12 weeks TIDieR description of the intervention: Brief name: a low GI diet plus exercise or a high GI diet plus exercise (HGI) for older adults Recipient: older (age around 66 years), obese, previously sedentary adults Why: investigate the effect of lifestyle intervention that included a low‐glycemic index diet combined with aerobic exercise on proinflammatory cytokine secretion in an at‐risk population such as the older obese who are more susceptible to type 2 diabetes and cardiovascular disease.  What (materials): "Diets were carefully formulated by a registered dietitian and were isocaloric to the individual requirements of subjects (screening resting metabolic rate multiplied by a sedentary activity factor of 1.2). The dietary macronutrient composition (including fiber) was matched between groups; however, the diets were designed so that LoGIX subjects received a diet corresponding to a GI of 40 arbitrary units (au), whereas HiGIX subjects were provided an 80‐au GI diet" What (procedures): diets were designed by a registered dietitian and all meals for the 12‐week intervention were provided to participants. Every session of exercise was fully supervised by an exercise physiologist. Who provided: registered dietitian and exercise physiologist How (mode of delivery; individual or group): individual and group Where: Cleveland; other specific locations were not described When and how much: 12‐week diet and exercise training intervention Tailoring: diets were designed by a registered dietitian and all meals for the 12‐week intervention were provided to participants. Every session of exercise was fully supervised by an exercise physiologist. Modification of intervention throughout the study: NR Strategies to improve or maintain intervention fidelity: adherence to the diet was determined via daily food container weigh backs plus a weekly counseling session with the study dietitian. Extent of intervention fidelity: NR Duration of intervention: 12 weeks Duration of follow‐up: 3 days pre and post‐intervention Run‐in period: NR
Outcomes	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: not available Endpoints quoted in publications Primary outcome measure(s): body weight, adiposity Secondary outcome measure(s): fat mass, fat‐free mass, systolic blood pressure, diastolic blood pressure, HbA1c, fasting plasma glucose, fasting plasma insulin, triglyceride, total cholesterol, HDL, LDL, dietary adherence Other outcome measure(s): not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight, adiposity Secondary outcome measure(s): insulin secretion Other outcome measure(s): not available
Study registration	Trial identifier: NR Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English  Funding: NR Declaration of interest: none to declare Publication status: peer‐reviewed journal
Stated aim of study	Quote: "In this study, we investigated the effects of consumption of a low‐GI diet or high‐GI diet combined with supervised exercise training for 12 wk on oral glucose tolerance in older, obese individuals. We examined physiologic changes in whole‐body insulin sensitivity and insulin and glucose‐dependent insulinotropic polypeptide (GIP) hormone secretion, which are components that are central to glucose clearance in the postprandial period. We hypothesized that a low‐GI diet in combination with exercise would elicit greater improvements in glucose metabolism than would a high‐GI diet in combination with exercise via larger alterations in insulin action and secretion and improved GIP secretion."
Notes	Contact with study authors: attempted on 23 April 2021. No reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quoted: "The study was conducted by using a randomized, controlled, parallel‐group, repeated‐measures design". Comment: randomisation method not stated. However, groups appear to have similar baseline characteristics.
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information about allocation concealment
Blinding of participants and personnel (performance bias) Anthropometric measures	Unclear risk	Comment: insufficient information about blinding of participants and study personnel
Blinding of participants and personnel (performance bias) Glycaemic control	Unclear risk	Comment: insufficient information about blinding of participants and study personnel
Blinding of participants and personnel (performance bias) Insulin action	Unclear risk	Comment:  insufficient information about blinding of participants and study personnel
Blinding of participants and personnel (performance bias) Cardiovascular risk factors	Unclear risk	Comment: insufficient information about blinding of participants and study personnel
Blinding of participants and personnel (performance bias) Dietary adherence	Unclear risk	Comment: insufficient information about blinding of participants and study personnel
Blinding of outcome assessment (detection bias) Anthropometric measures	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Glycaemic control	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Insulin action	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Cardiovascular risk factors	Low risk	Comment: insufficient information about blinding of outcome assessors, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Incomplete outcome data (attrition bias) Anthropometric measures	Low risk	Comment: total of 12 participants in each group. Two dropped out in the low GI group (1; failure to comply with  diet and exercise, 1; refusal of repeated testing). Plausible effect size  among missing outcomes was not enough to have a clinically relevant impact on observed effect size.
Incomplete outcome data (attrition bias) Glycaemic control	Low risk	Comment: total of 12 participants in each group. Two dropped out in the low GI group (1; failure to comply with  diet and exercise, 1; refusal of repeated testing). Plausible effect size  among missing outcomes was not enough to have a clinically relevant impact on observed effect size.
Incomplete outcome data (attrition bias) Insulin action	Low risk	Comment: total of 12 participants in each group. Two dropped out in the low GI group (1; failure to comply with  diet and exercise, 1; refusal of repeated testing). Plausible effect size  among missing outcomes was not enough to have a clinically relevant impact on observed effect size.
Incomplete outcome data (attrition bias) Cardiovascular risk factors	Low risk	Comment: total of 12 participants in each group. Two dropped out in the low GI group (1; failure to comply with  diet and exercise, 1; refusal of repeated testing). Plausible effect size  among missing outcomes was not enough to have a clinically relevant impact on observed effect size.
Incomplete outcome data (attrition bias) Dietary adherence	Low risk	Comment: total of 12 participants in each group. Two dropped out in the low GI group (1; failure to comply with  diet and exercise, 1; refusal of repeated testing). Plausible effect size  among missing outcomes was not enough to have a clinically relevant impact on observed effect size.
Selective reporting (reporting bias)	Low risk	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: not available Endpoints quoted in publications Primary outcome measure(s): body weight, adiposity Secondary outcome measure(s): fat mass, fat‐free mass, systolic blood pressure, diastolic blood pressure, HbA1c, fasting plasma glucose, fasting plasma insulin, triglycerice, total cholesterol, HDL, LDL, dietary adherence Other outcome measure(s): not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): body weight, adiposity Secondary outcome measure(s): insulin secretion Other outcome measure(s): not available Comments: the study protocol was unavailable, but it was clear that the published reports included all expected outcomes.
Other bias	Low risk	Comment: no other potential sources of bias detected.

Venn 2010.

Study characteristics
Methods	Study design: parallel randomised controlled trial Number of study centres: 1
Participants	Inclusion criteria: BMI ≥ 28 kg/m2,  fasting blood glucose concentration < 6.1 mmol/L and 2‐hour postload OGTT < 11.1 mmol/L, no diagnosis of chronic disease (diabetes mellitus, cancer, coronary heart disease) Exclusion criteria: pregnant, lactating, diabetic Diagnostic criteria: OGTT performed during screening Setting: community setting/free‐living  individuals Age group: adults Gender distribution: females and males Country/countries where study was performed: New Zealand
Interventions	Intervention(s): low GI diet  Diet was similar to the comparator group except participants were specifically instructed to consume 2 servings of pulses as a substitution for 2 servings of breads and cereals, and all other breads and cereals were to be wholegrain Comparator(s): high GI diet Diet followed the guidelines published by the National Heart Foundation of New Zealand, which included recommendations to eat each day at least 3 servings of vegetables and 2 servings of fruit; at least 6 servings of bread and cereals; at least 2 servings of reduced fat milk and milk products; 1 to 2 small servings of protein‐rich foods selected from lean meat, poultry, fish, seafood, and legumes; 1 to 2 tablespoons of monounsaturated or polyunsaturated fats and oil products; and small amounts of nuts and seeds TIDieR description of the intervention: Brief name: adherence to the New Zealand food pyramid or a diet high in wholegrains and legumes Recipient: overweight adults with an initial body mass index of > 28 kg/m2 Why: "Results from observational studies have shown that the type of carbohydrate consumed may play an important role in body weight regulation, with wholegrain intake being inversely associated with weight gain over time... In addition, high pulse (bean) intake has been associated with greater nutrient intake, a smaller waist circumference, and reduced systolic blood pressure in U.S. adults... Satiation may be attained at a lower energy intake through the consumption of low compared with high energy‐dense foods... A paucity of data is available on the effects of pulses on weight, particularly in the long term." What (materials): "The control group was instructed to follow the guidelines published by the National Heart Foundation of New Zealand, which included recommendations to eat each day at least 3 servings of vegetables and 2 servings of fruit; at least 6 servings of breads and cereals; at least 2 servings of reduced fat milk and milk products; 1 to 2 small servings of proteinrich foods selected from lean meat, poultry, fish, seafood, and legumes; 1 to 2 tablespoons of monounsaturated or polyunsaturated fats and oil products; and small amounts of nuts and seeds. The intervention group was given similar advice, except they were specifically instructed to consume 2 servings of pulses as a substitution for 2 servings of breads and cereals, and all other breads and cereals were to be wholegrain. One slice of bread (37 g), 30 g cereal, or 90 g pulses constituted a serving. All participants were strongly advised to stay within portion size guidelines as given by the National Heart Foundation of New Zealand. Anticipated energy intake based on the Heart Foundation guidelines was 7.2 MJ/day. Key foods for each diet were provided to participants fortnightly during the first 6 months." What (procedures): "Participants assigned to the intervention diet received rolled oats and rye, canned pulses (chickpeas, lentils, red kidney beans, butter beans, baked beans in a low energy sauce, mixed beans), and wheat and rye breads made with wholemeal flour and comprising around 20% by weight whole or kibbled grains. Participants assigned to the control group received cornflakes, cans of fruits and vegetables such as corn and tomatoes, and bread made with refined wheat flour. Cereals and bread provided to the intervention group tended to be of low glycemic index ( < 55), whereas the control group received more refined cereals and breads that tended to be medium to high glycemic index. Some flexibility was seen with each diet in the food items provided to accommodate individual preference and to allow for variety. During the first 6 months, participants attended cooking classes and supermarket tours, and they received dietary advice and recipe cards developed by a registered dietitian. Every 2 weeks, participants attended dietary counseling sessions in pairs, during which they were weighed and received dietary advice from a registered dietitian. Participants were encouraged to exercise for half an hour a day and were given a pedometer." Who provided: registered dietitian  How (mode of delivery; individual or group): "Participants attended dietary counseling sessions in pairs." Sessions were face to face. Where: "Participants attended supermarket tours." Other locations were not described.  When and how much: "Dietary counseling sessions were given every 2 weeks for the first 6 months... The first 6 months involved 2‐weekly counseling sessions and the provision of key foods, followed by 12 months during which participants had monthly contact with the study investigators." Tailoring: NR Modification of intervention throughout the study: NR Strategies to improve or maintain intervention fidelity: the first 6 months involved 2‐weekly counseling sessions and the provision of key foods, followed by 12 months during which participants had monthly contact with the study investigators. Extent of intervention fidelity: "Key foods for each diet were provided to participants fortnightly during the first 6 months." Duration of intervention: 72 weeks Duration of follow‐up: NR Run‐in period: NR
Outcomes	Endpoints quoted in trial document(s) (ClinicalTrials.gov, FDA/EMA document, manufacturer's website, published design paper) Source: ACTRN12605000537651 (www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=563) Primary outcome measure(s): weight loss Secondary outcome measure(s): blood lipids Other outcome measure(s): not available  Trial results available in trial register: not available  Endpoints quoted in publications Primary outcome measure(s): anthropometric measures (body weight, height, and waist circumference) Secondary outcome measure(s): plasma total cholesterol, HDL, LDL, triacylglycerol, systolic blood pressure, diastolic blood pressure, fasting glucose, dietary adherence  Other outcome measure(s): not available Endpoints quoted in abstract of publication(s) Primary outcome measure(s): weight loss Secondary outcome measure(s): blood pressure, triglycerides, waist circumference Other outcome measure(s): not available
Study registration	Trial identifier: ACTRN12605000537651 Study terminated early (for benefit/because of adverse events): no
Publication details	Language of publication: English  Funding: non‐commercial funding: New Zealand Foundation for Research, Science and Technology and the Lifestyle foods programme / commercial funding; Crop and Food Research Limited Declaration of interest: none to declare Publication status: peer‐reviewed journal
Stated aim of study	Quote: "The aim of our study was to investigate whether a diet high in whole grains and pulses would induce weight loss and maintenance, improve cardiovascular risk factors, and maintain micronutrient intakes to a greater extent than a high carbohydrate diet based on less specific advice as to the type of carbohydrate‐containing foods."
Notes	Contact with study authors: attempted on 21 April 2021. No reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Coin toss, unstratified" Comment: study authors achieved sequence generation using tossing of coin.
Allocation concealment (selection bias)	Unclear risk	Comment: insufficient information about allocation concealment
Blinding of participants and personnel (performance bias) Anthropometric measures	Unclear risk	Quote: "Open (masking not used)".  Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Glycaemic control	Unclear risk	Quote: "Open (masking not used)".  Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Cardiovascular risk factors	Unclear risk	Quote: "Open (masking not used)".  Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of participants and personnel (performance bias) Dietary adherence	Unclear risk	Quote: "Open (masking not used)".  Comment: complete blinding of both participants and study personnel is not possible due to the nature of the study.
Blinding of outcome assessment (detection bias) Anthropometric measures	Low risk	Quote: "Open (masking not used)" Comment: no blinding of outcome assessment, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Glycaemic control	Low risk	Quote: "Open (masking not used)" Comment: no blinding of outcome assessment, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Cardiovascular risk factors	Low risk	Quote: "Open (masking not used)" Comment: no blinding of outcome assessment, but we judge that laboratory index measures are unlikely to have been influenced by lack of blinding.
Blinding of outcome assessment (detection bias) Dietary adherence	High risk	Quote: "Three‐day weighed diet records (2 weekdays and 1 weekend day) were recorded by participants on 4 occasions." Comment: self‐reported dietary intake
Incomplete outcome data (attrition bias) Anthropometric measures	High risk	Quote: "Beyond 6 months, a greater rate of withdrawals lessens the assurance that we can place on the data. In particular, retention rates from 6 to 18 months declined considerably in the control group from 89% to 55%, and less so in the intervention group, from 92% to 81%." Comment: attrition was greater in the control group. Reasons for attrition varied between intervention and control group. Also, 37% of the control group dropped out after six months due to the diet not meeting their expectations, compared to 9% of the intervention group.
Incomplete outcome data (attrition bias) Glycaemic control	High risk	Quote: "Beyond 6 months, a greater rate of withdrawals lessens the assurance that we can place on the data. In particular, retention rates from 6 to 18 months declined considerably in the control group from 89% to 55%, and less so in the intervention group, from 92% to 81%."  Comment: attrition was greater in the control group. Reasons for attrition varied between intervention and control group. Also, 37% of the control group dropped out after six months due to the diet not meeting their expectations, compared to 9% of the intervention group.
Incomplete outcome data (attrition bias) Cardiovascular risk factors	High risk	Quote: "Beyond 6 months, a greater rate of withdrawals lessens the assurance that we can place on the data. In particular, retention rates from 6 to 18 months declined considerably in the control group from 89% to 55%, and less so in the intervention group, from 92% to 81%." Comment: attrition was greater in the control group. Reasons for attrition varied between intervention and control group. Also, 37% of the control group dropped out after six months due to the diet not meeting their expectations, compared to 9% of the intervention group.
Incomplete outcome data (attrition bias) Dietary adherence	High risk	Quote: "Beyond 6 months, a greater rate of withdrawals lessens the assurance that we can place on the data. In particular, retention rates from 6 to 18 months declined considerably in the control group from 89% to 55%, and less so in the intervention group, from 92% to 81%." Comment: attrition was greater in the control group. Reasons for attrition varied between intervention and control group. Also, 37% of the control group dropped out after six months due to the diet not meeting their expectations, compared to 9% of the intervention group.
Selective reporting (reporting bias)	Low risk	Comment: the study protocol was available and all the study's prespecified outcomes were reported.
Other bias	Low risk	Comment: no other potential sources of bias detected.

BMI: body mass index; CR: calorie restriction; DEXA: dual‐energy X‐ray absorptiometry; DRIs: Dietary Reference Intakes; FM: fat mass; FFM: fat free mass; GI: glycaemic index; GL: glycemic load; HbA1c: glycosylated haemoglobin A1c; HDL: high‐density lipoprotein; HiGIx: high glycemic index; HOMA‐IR: Homeostatic Model Assessment for Insulin Resistance; HS‐CRP: high‐sensitivity C‐reactive protein test; LDL: low‐density lipoprotein; LoGIX or LGI: low glycemic index; NIH: National Institutes of Health; NR: not reported; OGTT: oral glucose tolerance test; RDA: recommended daily allowance; TC: total cholesterol; TG: triglyceride; TEE: total energy expenditure; TIDieR: Template for Intervention Description and Replication; WC: waist circumference; WHO: World Heath Organization    

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
ACTRN12609000307202	Different co‐interventions in the study arms (one arm was prescribed red meat and the other white meat)
Agus 2000	Intervention duration of fewer than 8 weeks
Armeno 2011	Intervention and comparator groups were low GI diets
Aston 2008	Daily diet GI and GL above cutoff values
Astrup 2013	Intended for weight maintenance
Ball 2003	Intervention duration of fewer than 8 weeks
Bellisle 2007	Daily GI or GL of diets were not evaluated
Bouche 2002	Intervention duration of fewer than 8 weeks
Breymeyer 2016	Daily diet GL above cutoff value
Buscemi 2013	Daily diet GI and GL above cutoff values
Chang 2012	Intervention duration of fewer than 8 weeks
ChiCTR1800016786	Body mass index below cutoff value
Clapp 1998	Intervention duration of fewer than 8 weeks
Dumesnil 2001	Intervention duration of fewer than 8 weeks
Ebbeling 2003	Daily diet GI and GL above cutoff values
Ebbeling 2005	Daily diet GI and GL above cutoff values
Fechner 2020	Intervention duration of fewer than 8 weeks
Giardina 2017	Intended for weight maintenance
Handjieva‐Darlenska 2014	Daily GI or GL of diets were not evaluated
Hernandez‐Alonso 2019	Intended for weight maintenance
Hjorth 2017	Daily GI or GL of diets were not evaluated
Hu 2020	Intervention duration of fewer than 8 weeks
ISRCTN56834511	Intervention was not related to GI or GL
Jaffe 2007	Intervention was not related to GI or GL
Jakicic 2015	Intervention was not related to GI or GL
Jebb 2010	Daily diet GI above cutoff value
Jenkins 1987	Body mass index below cutoff value
Juraschek 2016	Intervention duration of fewer than 8 weeks
Karl 2015	Daily diet GI above cutoff value
Kirk 2012	Daily diet GI and GL above cutoff values
Klemsdal 2010	Daily GI or GL of diets were not evaluated
Kong 2014	Daily diet GI and GL above cutoff values
Krog‐Mikkelsen 2011	Daily diet GI above cutoff values
Maki 2007	Daily diet GI above cutoff values
Mediano 2012	Body mass index below cutoff value
Melanson 2012	Comparator group was not randomised
Mirza 2013	Daily diet GI and GL above cutoff values
Mogul 2016	Intervention was not related to GI or GL (hypocaloric carbohydrate modified diet alone, and in combination with metformin, and metformin plus low‐dose rosiglitazone)
NCT00143936	Intervention not related to GI or GL
NCT00147264	Daily diet GI and GL above cutoff values
NCT00324090	Daily diet GI above cutoff values
NCT00477477	Terminated due to inadequate enrolment and lack of funds
NCT00603655	Terminated due to higher dropout rate than expected
NCT01010841	Co‐intervention (medical food) in one of the intervention arms
NCT01206413	Body mass index below cutoff value
NCT01255228	Body mass index below cutoff value
NCT01358890	Body mass index below cutoff value
NCT01476436	Intervention not related to GI or GL
NCT01737034	Body mass index below cutoff value
NCT02630524	Intervention not related to GI or GL
NCT04145466	Intervention not related to GI or GL
NCT04581421	Intervention not related to GI or GL
Padwal 2007	Intervention not related to GI or GL
Pereira 2005	Weight loss was not an outcome. The time duration was different for the intervention and comparator groups.
Philippou 2008	Daily diet GI above cutoff values
Piatti 1993	Daily GI or GL of diets were not evaluated
Polacek 2006	All participants in the control group self‐eliminated
Rajabi 2015	Low GI diet was compared to medication (metformin), not a diet
Rhodes 2017	Intervention duration of fewer than 8 weeks
Rizkalla 2012	Intervention duration of fewer than 8 weeks
Sacks 2014	Intervention duration of fewer than 8 weeks
Salinardi 2012	Ineligible intervention (both study arms were low GL diets with different co‐interventions)
Saraf‐Bank 2016	Intervention not related to GI or GL
Schwarzfuchs 2012	Intervention not related to GI or GL
Shyam 2014	Body mass index below cutoff value
Sichieri 2007	Body mass index below cutoff value
Sloth 2004	Daily diet GI above cutoff value
Sun 2019	BMI below cutoff value
Van Horn 1986	Body mass index below cutoff value. GI of the diets was not assessed
Van  2014	Intended for weight maintenance
Walilko 2013	Intervention duration of fewer than 8 weeks
Weaver 2007	Intervention not related to GI or GL
Wolever 2002	Intended for weight maintenance

GI: glycaemic index; GL: glycaemic load

Characteristics of studies awaiting classification [ordered by study ID]

Chavez 2017.

Methods	Type of study: interventional (clinical trial) Allocation: randomised Intervention model: parallel assignment Masking: NR Primary purpose: treatment
Participants	Condition: obesity Estimated number of participants: NR Inclusion criteria: women of reproductive age diagnosed with obesity (BMI ≥ 30 kg/m2) Exclusion criteria: NR
Interventions	Intervention(s): hypocaloric diet, with a macronutrient distribution of 45% to 55% carbohydrate, 15% to 20% proteins and 30% lipids; foods with low or medium GI were recommended and to reduce the intake of industrialised foods with high‐fructose corn syrup Comparator(s): hypocaloric diet, with a distribution of macronutrients of 60% to 65% carbohydrate, 10% to 15% proteins and 25% lipids, without restriction of any kind of food
Outcomes	Primary outcome(s): anthropometric measurements (body weight, BMI, fat percentage, arm anthropometry) Secondary outcome(s): dietetic (24‐hour recalls, food frequency questionnaires), physical activity, and adherence to treatment  Other outcome(s): NR Relevant proposed outcome measures for SoF table: body weight, BMI
Study details	Study identifier: NR Study start date: NR Study completion date: NR Responsible party/principal investigator: Clío Chávez Palencia, University of Guadalajara, Mexico
Publication details	Conference abstract
Stated aim of study	Quote: "The objective was to compare the efficacy of a modified CH diet vs. a diet with a standard proportion of macronutrients within a program of reduced adiposity in obese women."
Notes	Author contacted; manuscript has not been completed.

NCT00940966.

Methods	Type of study: interventional (clinical trial) Allocation: randomised Intervention model: parallel assignment Masking: none (open‐label) Primary purpose: treatment
Participants	Condition: elevated triglycerides; systolic hypertension; insulin resistance; abdominal obesity Estimated number of participants: 40  Inclusion criteria: adolescents and young adults ages 13 to 18 with a BMI > 95% for age or over 30 for young adults, with pre‐existing metabolic syndrome Exclusion criteria: people on any chronic medication other than antihistamines, asthma medications, oral contraceptives, or diabetes medications, smoke more than 5 cigarettes/day, suffer from alcoholism or drug abuse, or have any significant abnormality not associated with metabolic syndrome on screening labs, currently taking Byetta, having familial hypercholesterolemia, pregnant or those desiring pregnancy
Interventions	Intervention(s):  low glycaemic diet Comparator(s):  standard American Diabetes Association (ADA) diet energy‐restricted, very‐low carbohydrate diet
Outcomes	Primary outcome(s): weight loss Secondary outcome(s): NR Other outcome(s): NR Relevant proposed outcome measures for SoF table: weight loss
Study details	Study identifier: NCT number: NCT00940966 Study start date: July 2006 Study completion date: May 2012 Responsible party/principal investigator:  Steven Sondike, MD
Publication details	Marked as 'completed' in ClinicalTrials.gov but no publication available.
Stated aim of study	Quote: "The purpose of this study is to determine the effectiveness of two different non‐energy restricted controlled carbohydrate programs with the American Diabetes Associations' diet on glycosylated hemoglobin and other diabetes risk factors in obese adolescents with metabolic syndrome, a constellation of symptoms associated with the development of type 2 diabetes and cardiovascular disease."
Notes	Principal investigator contacted but did not respond.

NCT01303757.

Methods	Type of study: interventional (clinical trial) Allocation: randomised Intervention model: parallel assignment Masking: single (outcomes assessor) Primary purpose: treatment
Participants	Condition: obesity and metabolic syndrome Estimated number of participants: 155 Inclusion criteria: aged 18 to 40 years, body mass index (BMI) ≥ 27 kg/m2,  body weight ≤ 300 lbs [136 kg], access to a working telephone,  clearance in writing from a primary care provider (i.e. physician or nurse practitioner) to rule out pre‐existing medical conditions, willing and able to attend group workshops (for dietary intervention) on specified evenings Exclusion criteria: physician diagnosis of a major medical illness or eating disorder, chronic use of any medication that may affect study outcomes (e.g. insulin‐sensitising agents), current smoking, physical, mental, or cognitive handicaps that prevent participation, another member of the family participating in the study, planning to relocate from the current area of residence, planning to become pregnant
Interventions	Intervention(s): low glycaemic load diet Comparator(s): low‐fat diet
Outcomes	Primary outcome(s): percent body fat by dual‐energy x‐ray absorptiometry (DEXA) Secondary outcome(s): triglyceride, high‐density lipoprotein (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, C‐reactive protein, plasminogen Activator Inhibitor‐1, fasting blood glucose, insulin resistance, blood pressure, trunk fat Other outcome(s): serum insulin concentration 30 minutes following a standard 75‐gram oral glucose load, metabolomic profile, insulin sensitivity, abdominal‐to‐total fat ratio, waist‐to‐hip ratio Relevant proposed outcome measures for SoF table: none
Study details	Study identifier:NCT01303757 Study start date: February 2011 Study completion date: December 2015 Responsible party/principal investigator: David S. Ludwig
Publication details	Marked as 'completed' in ClinicalTrials.gov but no publication available.
Stated aim of study	Quote: "The primary aim of the study is to examine insulin secretion as an effect modifier of the efficacy of a low‐fat vs. low‐glycemic load diet for weight loss among overweight/obese young adults in an 18‐month, prospectively stratified, multi‐center randomized controlled trial"
Notes	Author contacted; manuscript has not been completed due to Covid‐19 pandemic and other issues.

NCT01755962.

Methods	Type of study: interventional (clinical trial) Allocation: randomised Intervention model: factorial assignment Masking: none (open‐label) Primary purpose: treatment
Participants	Condition: obesity Estimated number of participants: 88 Inclusion criteria: 18 to 35 years old, BMI ≥ 30 kg/m2, and/or waist circumference ≥ 40 inches [101 cm] for males or ≥ 35 inches [89 cm] for females, in good health as determined by the screening visit and review of medical history Exclusion criteria: have a known heart arrhythmia and/or abnormalities found in electrocardiogram (ECG) reading or use of medications that influence cardiovascular function, have been in a weight loss or exercise programme in the 6 months prior to participation, use tobacco products, have a syndrome or are prescribed medications that may influence body composition, insulin action, or cardiovascular disease (e.g. polycystic ovary syndrome (PCOS), prednisone, methylphenidate, etc.), lactose or gluten intolerant, pregnant
Interventions	Intervention(s): low glycaemic diet, no exercise low glycaemic diet, resistance training Comparator(s): high glycaemic diet, no exercise high glycaemic diet, resistance training
Outcomes	Primary outcome(s): endothelial function as determined by brachial artery FMD Secondary outcome(s): monocyte inflammation, insulin sensitivity by oral glucose tolerance test, MAGE via Continuous Glucose Monitoring System  Other outcome(s): body composition (total fat mass, visceral fat, hepatic fat fraction, lean body mass) via DEXA and MRI, plasma and cellular biomarkers post pre and post 12 week intervention, RNA/protein levels via muscle and fat tissue collection  Relevant proposed outcome measures for SoF table: none
Study details	Study identifier: NCT01755962 Study start date: April 2012 Study completion date: December 2017 Responsible party/principal investigator: Catherine Carpenter
Publication details	Marked as 'completed' in ClinicalTrials.gov but no publication available.
Stated aim of study	NR
Notes	Principal investigator contacted but did not respond.

Slabber 1994.

Methods	Type of study: interventional (clinical trial) Allocation: randomised Intervention model: cross‐over assignment  Masking: NR Primary purpose: treatment
Participants	Condition: overweight Estimated number of participants: 40 Inclusion criteria: hyperinsulinaemic when their fasting and stimulated insulin concentrations (after 75 g oral glucose) were compared with those of an age‐matched reference group (n = 15) of healthy volunteer females (P < 0.001). Exclusion criteria: fasting blood sugar > 5.8 or < 3.33 mmol/L, or > 11.0 and > 7.7 mmol/L, respectively, 30 and 120 minutes after 75 g oral glucose.
Interventions	Intervention(s): low insulin response diet  Comparator(s): conventionally balanced diet
Outcomes	Primary outcome(s): weight, BMI Secondary outcome(s): blood glucose, insulin, C‐peptide Other outcome(s): NR Relevant proposed outcome measures for SoF table: body weight, BMI
Study details	Study identifier: NR Study start date: NR Study completion date: NR Responsible party/principal investigator: Marthinette Slabber, University of the Orange Free State, South Africa
Publication details	Published in peer‐reviewed journal
Stated aim of study	Quote: "Our aim was to compare the long‐term (12 wk) effects of the ID with those of a balanced normal energy‐restricted diet (ND) in hyperinsulinemic obese females"
Notes	Not possible to clarify if the study meets inclusion criteria as the GI or GL values of the diets are not described. Unable to retrieve any of the authors' contact information.

BMI: body mass index; CH: carbohydrate; DEXA: dual‐energy X‐ray absorptiometry; FMD: flow‐mediated dilation; GI: glycaemic index; GL: glycaemic load; ID: low insulin response; MAGE: mean amplitude of glycaemic excursion; MRI: magnetic resonance imaging; NR: not reported 

Characteristics of ongoing studies [ordered by study ID]

CTRI/2020/11/029252.

Study name	Low glycemic diet in obese children
Methods	Randomised, parallel‐group trial
Participants	Children between 9 and 16 years old
Interventions	Low glycaemic diet: "Parents will be educated about glycemic index (GI) and the GI of various food items, the benefits of a low GI diet. Parents will be asked to change the flour used to make chapattis to LGI flour consisting of a mixture of jowar, ragi and chana atta (1:1:1) and add this atta mix to the normal wheat flour in ratio 1:1. Child will be given an ad‐libitum low GI index diet chart. Mothers will be given low GI recipes for snacks with traditional Indian millets like amaranth, jowar, ragi, buckwheat flour. Home based 7 day sample cyclical menu will be given according to the preferred choices and family food pattern."  Standard treatment: "The knowledge, practices and attitude of the patient and family will be studied by standard questionnaires. Lifestyle education programme based on evidence‐based guidelines (2 sessions of 1 hour each) will be given to both groups consisting of information on healthy diet, benefit of physical activity and behavioural methods to restrict over‐eating. Both groups will be advised to Restrict sugary beverages, colas and junk food, refined carbohydrates like maida. Increase intake of fresh fruits, salads and vegetables. Control arm Child will be given a diet chart based on RDA with reduction of 10% calories. Home based 7 day sample cyclical menu will be given according to the preferred choices and family food pattern."
Outcomes	Primary outcome: "Reduction of BMI by 1 kg/m2" Secondary outcome: "Laboratory investigations: fasting insulin, blood sugar, oral glucose tolerance test, HOMA‐IR, lipid profile, markers of inflammation (HS‐CRP, TNF‐alpha, IL‐6), adiponectin, liver function tests. Body composition analysis by DEXA scan for calculation of fat‐mass"
Starting date	19‐01‐2021
Contact information	Rajni Sharma, Department of Pediatrics, All India Institute of Medical Sciences, drrajnisharma@yahoo.com
Study identifier	‐
Official title	The effect of low glycemic index diet in the form of traditional Indian millets in obese children: a randomized controlled trial
Stated purpose of study	‐
Notes	‐

BMI: body mass index; DEXA: dual‐energy X‐ray absorptiometry; GI: glycaemic index; HOMA‐IR: Homeostatic Model Assessment for Insulin Resistance; HS‐CRP: high‐sensitivity C‐reactive protein test; IL‐6: interleukin 6; LGI: low glycaemic index; RDA: recommended daily allowance; TNF‐alpha: tumour necrosis factor alpha

Differences between protocol and review

This is an update of a previous Cochrane Review (Thomas 2007). 

We have updated the criteria for defining low GI or GL diets by adding the daily cutoff values to avoid overlapping of these values between low GI or GL diets with the comparison diets. 

As more trials are now available, we excluded short‐term studies and included only those of at least eight weeks' duration. 

We added dietary adherence as a secondary outcome in this updated review as it indicates the extent to which the diets are followed or practised by the participants. 

The editorial base changed the review template for their reviews; we adjusted our update to reflect these new methods, as follows.

• Data extraction and management: we incorporated all the data extracted into our Excel spreadsheets into the main body of the review, which are now described in Data extraction and management.

• Assessment of heterogeneity: we updated this section based on the guidance from the Cochrane Handbook, providing ranges for the interpretation of I².

• Data synthesis: we updated this section according to the guidance from the Cochrane Handbook, highlighting the use of random‐effect models for the primary analysis.

• Subgroup analysis: we added details on the pitfalls of the interpretation of subgroup analysis, as described in the Cochrane Handbook.

• Sensitivity analysis: we removed the intention to test "the robustness of results by repeating the analyses using different measures of effect size (i.e. RR, OR, etc.) and different statistical models (fixed‐effect and random‐effects models)", for consistency with our update in Data synthesis.

Contributions of authors

All review authors read and approved the final review update draft.

Khadidja Chekima (CK): development, acquisition of study reports, study selection, data extraction, data analysis, data interpretation, drafted the review, and future review updates.

See Wan Yan (YSW): development, acquisition of study reports, study selection, data extraction, data analysis, data interpretation, and future review updates.

Shaun Wen Huey Lee (SLWH): development, acquisition of study reports, study selection, data extraction, data analysis, data interpretation, and future review updates.

Tziak Ze Wong (WTZ): development, acquisition of study reports, data extraction, data analysis, data interpretation, and future review updates.

Mohd Ismail Noor (NMI): drafted the review, acquisition of study reports, data interpretation, and future review updates.

Yasmin Beng Houi Ooi (OYBH): development, acquisition of study reports,  data extraction, data analysis, data interpretation, and future review updates.

Maria‐Inti Metzendorf (MIM): drafted and conducted searches; reviewed draft.

Nai Ming Lai (LNM): drafted the review, acquisition of study reports, study selection, data extraction, data analysis, data interpretation, and future review updates.

Sources of support

Internal sources

• Taylor's University, Malaysia

  Taylor's PhD Scholarship was awarded to Khadidja Chekima

External sources

• None, Other

  Did not receive any external support

Declarations of interest

Khadidja Chekima: none known

Shaun Wen Huey Lee: none known

Tziak Ze Wong: none known

Mohd Ismail Noor: none known

Yasmin Beng Houi Ooi: none known

See Wan Yan: none known

Maria‐Inti Metzendorf: no known conflict of interest. MIM is an information specialist of the Cochrane Metabolic and Endocrine Disorders Group, but she was excluded from the editorial processing of this article.

Nai Ming Lai: none known

New search for studies and content updated (conclusions changed)