Application of nutrition interventions with GLP-1 based therapies: A narrative review of the challenges and solutions

Abstract

Background

Obesity is a heterogeneous systemic chronic disease associated with excess adiposity and a complex etiology and is increasing in prevalence worldwide. Initially used to treat type 2 diabetes mellitus, glucagon-like peptide-1 (GLP-1) based therapies are now widely prescribed for individuals with overweight and obesity as an adjunct to a reduced-calorie diet and increased physical activity. However, despite their impressive weight reduction capabilities, many patients on GLP-1 based therapies do not receive appropriate nutrition advice and struggle to maintain their weight reduction.

Methods

This narrative review explores and summarizes existing literature on the challenges associated with nutrition intake in people with obesity taking GLP-1 based therapies and practical applications of nutrition and lifestyle interventions for the management of these individuals to ensure their best long-term health outcomes.

Results

Delivering optimal nutrition management to people with obesity treated with GLP-1 based therapies presents healthcare providers with many challenges including addressing the impact of obesity and weight reduction on body composition (particularly muscle mass loss and risk of sarcopenic obesity), and poor nutrition. Physicians should work with dietitians and other healthcare providers to deliver comprehensive lifestyle counselling that is patient-centered, aligning with the needs and preferences of the individual. This should include advice on: timely and appropriate nutrition that centers on adequate macronutrient, micronutrient and fluid intake, particularly increased protein intake alongside resistance training for the preservation of muscle mass; mental health; sleep hygiene, physical activity; and medication adherence and persistence. Evidence-based nutrition guidelines can also provide an important framework for healthcare professionals, helping to ensure nutrition advice is consistent and based on rigorous scientific research.

Conclusions

Our findings underscore the importance of ensuring that patients treated with GLP-1 based therapies are closely monitored and provided with comprehensive nutrition and lifestyle support to ensure they achieve the best long-term health outcomes.

Graphical abstract

1. Introduction

Obesity is a global epidemic, increasing in prevalence year to year [1]. According to the World Health Organization (WHO), the percentage of adults aged 18 years of age and older living with obesity more than doubled to 16 % during the period from 1990 to 2022 [1]. In the United States (US), a country with one of the highest prevalence rates, obesity affects more than 4 in 10 adults, and nearly 1 in 10 Americans have severe obesity [2,3].

Obesity is a heterogeneous systemic chronic disease associated with excess adiposity and has a complex etiology [4]. An imbalance between food intake, metabolism and energy expenditure is the principal mechanism responsible for excess weight gain and arises from a complex interplay between genetic and epigenetic factors and an obesogenic environment [3,5]. A global commission published in 2025 highlighted the limitations of the traditional approach of defining obesity based on body mass index (BMI) alone (e.g. >30 kg/m² for people of European descent) [4]. Although BMI can be used to identify an individual's level of risk for morbidity, it does not differentiate between fat and lean mass or reflect differences in body fat distribution and is not indicative of the functional state of tissues and organs or the general health of an individual. Consequently, BMI can over diagnose or underdiagnose obesity depending on the individual. For example, athletes with increased skeletal muscle mass may have a high BMI but low adipose tissue, whereas other individuals may have a BMI within the normal range but have excess body fat (normal weight obesity) [4].

The negative health consequences of obesity include an increased risk of a wide spectrum of diseases including type 2 diabetes (T2DM), other cardiovascular disease risk factors (e.g., hypertension and dyslipidemia), cardiovascular disease, thromboembolic events, musculoskeletal disorders, fatty liver, chronic kidney disease, certain cancers, mental health disorders, as well as sleep apnea, limited mobility, and diminished quality of life [[6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16]].

In addition to its impact on physical and mental well-being, obesity significantly impacts healthcare costs and overall societal expenses [17,18]. Annual obesity-related medical care costs in the US (2019 dollars), have been estimated at ∼$173 billion, with annual medical costs for adults with obesity $1861 higher per person than for adults of a healthy weight [18]. Further economic burden can also be attributed to the substantial indirect costs associated with obesity including those related to absenteeism, presenteeism (reduced productivity at work), short- and long-term disability, premature mortality and worker compensation [17,19].

Since their first regulatory approval in 2005, glucagon-like peptide-1 (GLP-1) based therapies have played an important role in the treatment of patients with T2DM, improving glycemic control, reducing body weight, and reducing the risk of cardiovascular disease [20]. More recently, GLP-1 based therapies have demonstrated efficacy for weight management in patients without T2DM, leading to their approval as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management [[21], [22], [23], [24]]. However, despite the widespread use of GLP-1 based therapies, many patients do not receive appropriate dietary or nutritional advice and struggle to achieve the intended weight reduction partly due to the adverse effects of treatment [23,25,26].

This narrative review aims to explore the existing literature on the challenges associated with nutrition intake in people with obesity taking GLP-1 based therapies and practical applications of nutrition and lifestyle interventions for the management of these individuals to ensure their best long-term health outcomes.

2. Methods

For this narrative review we conducted a search of PubMed and Google Scholar for the period February 2020 to February 2025. Several keywords were employed in the search including: GLP-1 based therapy, adherence, side effects, outcomes, dietary/nutrition intake, protein intake, hydration, food plans, body composition, sarcopenia, sarcopenic obesity, guidelines, recommendations, lifestyle, physical activity, exercise, mental health, health outcomes, dietitian, and multidisciplinary team. Systematic reviews, randomized controlled trials, observational studies, narrative reviews and guidelines addressing the topic of nutrition intake and management of people with obesity were considered potentially eligible for inclusion. Key references identified during development of the review (not identified in our search) that were supportive of the topics under discussion were also included where appropriate. This included a joint statement from four clinical and research societies on nutrition priorities to support GLP-1 based therapy for obesity that was published in May 2025, after completion of our literature search [27]. Articles not available in English, conference abstracts, and case reports were excluded.

3. Pharmacotherapy for obesity: GLP-1 based therapies

Three GLP-1 based therapies, liraglutide and semaglutide (both GLP-1 receptor agonists) and tirzepatide (a glucose-dependent insulinotropic polypeptide [GIP]/GLP-1 dual receptor agonist) are currently approved by the US Food and Drug Administration for the treatment of overweight and obesity as an adjunct to a reduced-calorie diet and increased physical activity [[21], [22], [23]]. Other classes of obesity medications, including the centrally acting medications phentermine-topiramate, naltrexone-bupropion, phentermine (available since the 1960s) and the gastrointestinal lipase inhibitor orlistat are associated with a weight reduction of ∼5–10 % of mean body weight [28]. However, the significantly greater weight reduction associated with GLP-1 based therapies and their proven health benefits (e.g., reduction in cardiovascular disease with semaglutide [29] and improved sleep apnea with tirzepatide [30]), as well as a wider acceptance that medication is needed for sustained weight reduction success, has triggered a rapid surge in their uptake [31].

Beyond their indicated uses for treatment of T2DM, liraglutide and semaglutide are recommended for the treatment of adults and children aged 12 years and over with overweight and obesity [32,33]; tirzepatide is only recommended for the treatment of adults with overweight and obesity as the adolescent trials are still ongoing [34]. Administration is by subcutaneous injection given either weekly (tirzepatide, semaglutide) or daily (liraglutide).

By mimicking the actions of the enteropancreatic hormones GLP-1 (liraglutide, and semaglutide) or GLP-1 and GIP (tirzepatide), these drugs modify central appetite regulation and can achieve significant weight reductions as high as ∼25 % compared with placebo [21,[35], [36], [37], [38], [39]]. In pivotal Phase 3 studies in patients with overweight or obesity and without diabetes, percentage weight reduction from baseline was 20.9 % with tirzepatide (15 mg once weekly) after 72 weeks of treatment [40], 14.9 % with semaglutide (2.4 mg once weekly) after 68 weeks of treatment [41], and 8.0 % with liraglutide (3.0 mg once daily) after 56 weeks of treatment [42]. In addition to achieving substantial weight reduction, GLP-1 based therapies also provide other health benefits in patients with obesity. Studies have demonstrated cardiovascular benefits with GLP-1 based therapies in patients with pre-existing cardiovascular disease or cardiovascular risk factors [29,43], including patients with heart failure with preserved ejection fraction and obesity [44,45]. In addition, clinically meaningful reductions in sleep-disordered breathing have been reported in patients with moderate-to-severe obstructive sleep apnea and obesity, including a reduction in the number of apneas and hypopneas, and improvements in hypoxic burden and patient-reported sleep impairment and disturbance [30].

While GLP-1 based therapies are highly effective at managing weight reduction, gastrointestinal (GI) side effects, including nausea (25–44 %), diarrhea (19–32 %), vomiting (8–25 %), constipation (12–23 %) and abdominal pain (5–10 %), were common in pivotal Phase 3 studies, although generally transient in nature [[40], [41], [42],46]; Other side effects including fatigue, injection site reaction, hypoglycemia and headaches may also occur [21,23,37,47]. In addition, GLP-1 based therapy is associated with changes in body composition and nutrition intake (described in more detail later in this review) [48,49].

4. Effect of obesity medications on muscle mass

4.1. Understanding body composition changes during weight reduction

Muscle mass plays a crucial role in maintaining physical function, metabolic health, bone-remodeling and thermoregulation and also serves as a major repository for the storage of glycogen fat and protein. The consequences of significant muscle loss are wide ranging and include metabolic changes, functional impairment and reduced quality of life [50]. In an ideal situation, weight reduction should be derived exclusively from loss of fat mass (FM) [51]; however, weight reduction in general is associated with reductions in both lean body mass (LBM) and fat mass (FM), which together with bone make up total body mass (TBM). LBM is made up of skeletal muscle, internal organs and water (i.e. TBM minus FM and bone mineral content), with skeletal muscle comprising the majority of LBM (>50 %). FFM is LBM with the addition of bone [Fig. 1] [50,52].

Fig. 1.

Schematic of body composition.

In an overview of weight reduction clinical trials, percent of total weight reduction achieved with very low calorie, low carbohydrate, low fat and high fiber diets comprised approximately 75 % FM reduction and approximately 25 % LBM reduction. A high protein diet (>0.8 g protein/kg bodyweight/day) was associated with the lowest reduction in LBM (|11 % of total weight reduction), and the highest reduction in FM reduction (89 % of total weight reduction) [Fig. 2] [53]. Concern has been raised about the possibility of excessive reduction in LBM, associated with the magnitude of weight reduction and decreased energy intake experienced with GLP-1 therapies [49,54]. This can have potentially negative short- and long-term consequences for health and physical function and highlights the importance of maintaining protein intake during weight reduction (discussed in more detail later).

Fig. 2.

Effect of weight reduction interventions on lean body mass

Footnotes: GLP-1RA, glucagon-like peptide-1 receptor agonists; LBM, lean body mass.

4.2. Potential risk for sarcopenic obesity

Many individuals with obesity have increased muscle mass strength compared with those with normal weight because of their larger body weight load which stimulates muscle growth [55]. However, although people with obesity may have higher absolute muscle strength, they may exhibit lower relative strength per unit of TBM compared with those without obesity [Fig. 2]. Reduced mobility, neural adaptions and structural changes to muscle tissue may all contribute to this relative weakness [55]. Furthermore, loss of skeletal muscle mass and strength and reduced physical performance is common in older adults (>65 years) and is often paralleled by a relative or absolute increase in FM [56,57]. Finally, it is not uncommon to find patients with obesity and diminished mobility to have both an increase in body fat and decrease in lean (muscle) mass [58].

Co-existence of low skeletal muscle mass and low muscle function with excess adiposity is referred to as sarcopenic obesity and should be considered a unique clinical condition, distinct from obesity or sarcopenia (i.e. loss of muscle mass/strength) alone [56,59]. According to a consensus statement developed by international experts, diagnosis should involve screening for both obesity and sarcopenia followed by assessment of muscle mass, strength and function, and altered body composition; confirmation of a diagnosis of sarcopenic obesity is then established by the presence of excess adiposity and low skeletal muscle mass or related body compartments [56].

Sarcopenic obesity affects almost 30 million adults in the US with prevalence increasing with age and among those with prediabetes, T2DM, non-alcoholic fatty liver disease with fibrosis, and post-bariatric surgery [58]. The clinical consequences of sarcopenic obesity are wide ranging with affected individuals often experiencing worse survival and morbidity, as well as metabolic disturbances, increased cancer risk, decreased quality of life and a range of geriatric syndromes including cognitive impairment, functional limitations and frailty [59,60].

The pathophysiology of sarcopenic obesity involves an intricate relationship between multiple factors including genetic, environmental and social factors, physical inactivity, malnutrition (i.e. inadequate protein/nutrient intake), low-grade inflammation, oxidative stress, insulin resistance, and hormonal imbalances which independently and synergistically impact both muscle mass and fat tissue resulting in a decline in muscle mass and strength and a gain in adipose tissue [59,61]. The impact of these factors is further compounded by older age, and presence of comorbidities, as well by pre-existing low muscle mass, sarcopenia, a history of weight recycling and calorie restriction [Fig. 2] [49].

Patients taking obesity medications, particularly older individuals, are also at risk of developing sarcopenic obesity due to reduction in LBM, with the proportion of total weight reduction due to decreased LBM reported to typically lie between 25 and 60 % in clinical trials of GLP-1 based therapies [Fig. 2] [54,62]. In the STEP-1 trial (Semaglutide Treatment Effect in People with obesity) and the SURMOUNT-1 trial (A study of tirzepatide in participants with obesity or overweight with weight-related comorbidities) evaluating GLP-1 based therapies for the treatment of obesity, the estimated loss of skeletal muscle was ≥10 % during 68–72 weeks of treatment; this has been equated approximately to the average decline in muscle mass that occurs during 20 years of ageing in adults aged above 30 years [49].

5. Effect of obesity medications on nutrition intake

5.1. Macronutrients, micronutrients and fluids

People with obesity may have risk factors for malnutrition and micronutrient deficiencies which are exacerbated when they embark on weight reduction diets and obesity medications [48,63,64]. A number of studies have reported a higher incidence of nutrient deficiencies among people with excessive body weight compared with people with normal body weight of the same age and sex [65]. As well as experiencing deficits in key macronutrients (i.e. protein, fiber and unsaturated fats), people with obesity typically have high rates of micronutrient deficiencies including deficiencies in vitamin A, vitamin D, vitamins B1 (thiamine) and B12 (cobalamin), folate, iron, calcium, magnesium and zinc [63,64].

Nutrient deficiencies associated with obesity may be partly due to consumption of a poor-quality diet that is high in calories but has a low nutrient density; this is a particular problem among people of a lower socioeconomic status who are at increased risk of living in “food deserts” [66]. However, a variety of other risk factors have also been implicated in the development of malnutrition in people with obesity including defective storage and bioavailability of nutrients, small intestine bacterial overgrowth, low grade chronic inflammation (leading to oxidative stress and increased anti-oxidant utilization), older age and excessive consumption of simple sugars, milk and fat. Furthermore, a history of bariatric surgery, the presence of comorbid disease (including chronic kidney disease or heart failure), and use of medications that impact nutrient metabolism and absorption (e.g. metformin, loop diuretics and proton pump inhibitors) have also been implicated [63,64]. This combined burden of obesity and malnutrition is associated with significant risks including exacerbation of comorbid disease, increased risk of sarcopenic obesity, immune dysfunction, delayed wound healing, anemia, metabolic disturbances and impaired mood and cognition [63,64].

GLP-1 based therapies act to decrease appetite and food consumption and thereby affect nutrition intake, with a reduction in calorie intake of up to 40 % reported in patients receiving a GLP-1 based therapy compared with those receiving placebo [Fig. 3] [48]. Data suggest that this effect of GLP-1 based therapies is mediated via decreased intake of high-calorie and processed foods possibly as a consequence of enhanced sensitivity to sweet tastes and reduced pleasure responses to fatty foods, although further research is needed to confirm this [67]. However, in addition to their potential positive effect on food preferences [68], GLP-1 based therapies may also impact food choices in such a way that could result in reduced dietary quality. For example, GLP-1 based therapy has been associated with a reduction in the consumption of meat (beef, pork and fish) and therefore reduced protein intake, which can lead ultimately to accelerated reduction of LBM and reduced muscle mass, strength and function [67]. In a large retrospective analysis of patients with T2DM who had received GLP-1 based therapy (n = 461,382), over 20 % of patients had nutritional deficiencies diagnosed within one year of starting treatment, with Vitamin D deficiency the most common (14 % of patients at one year), and 3 % of patients were diagnosed with muscle loss within one year [69].

Fig. 3.

Effect of obesity medications on nutritional intake

Footnote: eGFR, estimated glomerular filtration rate; LBM, lean body mass.

Available data from animal and clinical studies also suggest that GLP-1 agonism may reduce thirst and water intake [Fig. 3] [70,71]. Treatment of patients with primary polydipsia with the GLP-1 based therapy dulaglutide for three weeks was associated with a 17 % reduction in fluid intake (p = 0.002) and a reduction in acute thirst perception compared with placebo [71]. Furthermore, reduced consumption of healthy foods such as fruit and vegetables will decrease water intake as many of these foods comprise approximately 90 % water [72]. This highlights the importance of fruit and vegetable intake among those treated with GLP-1 based therapy, both from a micronutrient standpoint and a hydration standpoint. Consequences of dehydration include a reduction in estimated glomerular filtration rate and an increase in creatinine and potassium levels which may negatively impact renal function; this may be of particular concern in older patients who often experience a natural decline in renal function with age and may be more susceptible to the effects of dehydration. Further studies in humans are required to determine whether the effects of GLP-1 based therapies on polydipsia and thirst perception also occur in people with obesity.

6. Factors to ensure successful long-term nutrition care and positive outcomes during treatment with obesity medications

6.1. Preserving muscle mass during weight reduction

6.1.1. Higher protein intake

Protein plays a central role in the preservation of LBM and a high protein diet that exceeds the recommended 0.8 g protein/kg bodyweight/day is the best option to mitigate the reduction in LBM, with patients encouraged to increase their protein intake to maintain and recover muscle mass and function over the long term [51,59,73,74].

The current recommended protein intake for a patient on obesity medication is 1–1.5 g of protein per kilo of body weight, with the higher end of this range (1.2–1.5 g protein/kg bodyweight/day) recommended for older individuals (>65 years) and those with multiple comorbidities [49,59,61,73]. Among individuals with overweight or obesity, calculating the recommended protein intake using their actual bodyweight may lead to a significant overestimation of protein requirement. Basing this calculation on corrected bodyweight (adjusted or ideal) or FFM, or setting an absolute protein target of 80–120 g/day (or 16 %–24 % energy on a 2000 kcal/day diet) have been proposed as alternative approaches, although a clear consensus on the optimal method has yet to be reached [27]. Where possible, protein intake should be distributed evenly across the day (versus skewed) to achieve optimal anabolic responses and FFM preservation [75]. Recommended sources of protein should be of high quality (based on essential amino acid content and protein digestibility) to support muscle protein synthesis, and include fish, poultry, lean meat, dairy, egg whites, nuts, seeds and soy; protein sources high in saturated fats (e.g. non-lean pork, lamb and beef and processed meat) should be avoided [49,73,75]. If higher protein intake cannot be achieved through diet alone, then protein supplementation from a reputable source may be considered [54,75]. Protein intake should be closely monitored in people with renal insufficiency (proteinuria and estimated glomerular filtration rate <60 mL/min) and specialist renal advice should be sort before increasing protein intake for these patients [73].

As well as having beneficial effects on muscle mass and function, a high protein diet also enhances satiety by elevating blood amino acid concentrations and increasing and decreasing levels of anorexigenic and orexigenic hormones, respectively [76,77]. This facilitates weight reduction through reduced energy consumption, and increased thermogenesis and sleeping metabolic rate, which further enhance energy expenditure.

6.1.2. Resistance training

In addition to higher protein intake, addressing physical inactivity through regular exercise can further help to preserve muscle mass and functionality [49,54,59,74,78]. Available evidence suggest that this benefit is mediated via exercise-induced muscle contractions which improve muscle protein synthesis through stimulation of nitric oxide production and increased insulin sensitivity [59].

Specifically, resistance training has been shown to have a positive effect on body composition and muscle strength in people with overweight or obesity [79,80]. A systematic review found that resistance training (2–3 times/week, lasting ≥8 weeks) had a beneficial effect on body composition via a reduction in percent body fat and was also associated with improvements in muscle mass, muscle strength and gait speed in older adults with sarcopenia and obesity [79]. In an earlier systematic review, a pooled analysis suggested that resistance training (2–3 sessions/week, lasting ≥4 weeks) had a large benefit on muscle strength and a moderate effect on physical function in adults with overweight and obesity, although the effect on muscle power was deemed less certain [80].

The importance of resistance training for the preservation of muscle during weight reduction is reflected in several guidelines which recommend that patients with obesity undertake resistance training during weight reduction therapy [[81], [82], [83], [84]]. Resistance training/muscle strengthening exercises at least two times per week is the recommended goal [81]. In addition, combining resistance exercise training with protein supplementation may promote LBM gain and increase muscle strength compared with resistance training alone in older adults [85] and may be more effective than protein supplementation alone in this respect [86].

6.1.3. Pharmacological approaches

There are currently no approved drugs for the treatment of sarcopenic obesity. However, several pharmacological interventions are in development and may have an important role in the preservation of lean muscle mass in the future [49,87]. These include agents that target the myostatin/activin signaling pathway, for example bimagrumab which is a monoclonal antibody that binds to the activin type II receptor to prevent the action of natural ligands that negatively regulate skeletal muscle growth [88], and selective androgen receptor modulators that counteract the decline in androgen levels and muscle loss associated with aging and other conditions [89]. Other unproven, investigational approaches include combining GLP-1 based therapies with glucagon or amylin analogues to potentially lessen loss of lean mass [90].

6.1.4. Importance of measuring muscle mass and muscle strength

Assessment of muscle mass and function and physical performance can provide valuable information for individual's with sarcopenic obesity who are at high risk of losing muscle mass and help guide their obesity management [91]. Muscle mass can be measured using bioelectrical impedance analysis (BIA) or imaging techniques including dual X-ray absorptiometry, magnetic resonance imaging and less frequently, computerized tomography [49,51,59,92]. Additionally, measuring body composition (i.e., body fat and muscle mass) using BIA can aid patient understanding of the importance of focusing on preservation of muscle mass and increase patient engagement in the weight management process [93]. Commonly used measures of muscle function and strength include the handgrip, knee flexion/extension, sit-to-stand and 30-s chair stand tests [51,59,92].

6.2. Multidisciplinary teams

Optimization of nutrition quality can be achieved through increased interprofessional collaboration between clinicians and dietitians [94]. Many physicians do not receive adequate nutrition training and are unable to provide appropriate dietary advice and support to people with obesity [95,96]. This lack of training may stem from medical school curriculums which often give limited priority to nutrition education, and the fact that medical schools may not have a faculty devoted to the subject [95]. Among 235 primary care physicians in Sweden surveyed on their knowledge about obesity, almost one third (n = 72) confessed that their knowledge of weight management was insufficient and 40 % believed they lacked education in effective communication about obesity and weight management [96].

As highly skilled healthcare practitioners specializing in nutrition and the treatment of obesity and obesity-related disease, registered dietitian nutritionists are well placed to play a key role in educating physicians on nutrition throughout their training and practice. Furthermore, exposure to dietitians during medical school and continuing medical education may also increase physician awareness of the important advisory role of dietitians in providing expertise and guidance on nutrition and dietary needs to patients with obesity; this may ultimately promote improved collaboration by encouraging physicians to refer their patients to a dietitian [94].

6.2.1. Role of the dietitian

Patient referral to a dietitian as part of ongoing long-term multidisciplinary team support is widely accepted and considered crucial to ensure that patients with obesity receive optimal nutrition advice. Dietitians recognize the complexity of overweight and obesity, and are able to individualize and deliver nutrition interventions based upon a shared decision-making process in an inclusive, compassionate, and client-centered manner [[97], [98], [99], [100], [101], [102]].

Greater involvement of dietitians in patient care has been shown to improve nutrition-related clinical outcomes. In a systematic review of 62 randomized controlled trials, patients with overweight or obesity who received counselling from a dietitian had a greater reduction in BMI (mean difference −1.5 kg/m²; 95 % CI: 1.74, −1.26), percent weight reduction (−4.01 %; 95 % CI: 5.26, −2.75), waist circumference (−3.45 cm; 95 % CI: 4.39, −2.51) and blood pressure (systolic: 3.04 mmHg; 95 % CI: 5.10, −0.98; diastolic: 1.99 mmHg; 95 % CI: 3.02, −0.96), and improvement in mental and physical quality of life measured using the SF-36 tool compared with patients who received usual care or no intervention [103]. In addition, other studies have reported improvements in risk factors for cardiometabolic disease including reductions in dyslipidemia (total cholesterol, low-density lipoprotein and triglycerides), blood pressure, glycosylated hemoglobin, fasting blood glucose and insulin resistance following counselling by a dietitian and/or implementation of weight management programs [[104], [105], [106]].

6.2.2. Nutrition assessment

Appropriate nutrition or dietary assessment, preferably by a registered dietitian, plays a central role in the management of people with obesity [27,98,102]. Nutrition assessment can help identify individuals who are at increased risk of nutrition deficiencies and ultimately prevent severe nutrition and medical complications that may arise as a result of the decreased food intake that occurs when a patient embarks on treatment with a GLP-1 based therapy [63,102].

Nutrition assessment should be conducted prior to treatment with an obesity medication and include a thorough assessment of macronutrient and micronutrient intake and consumption of specific food groups, together with an evaluation of the patient's water intake and hydration, which is particularly important for older individuals [63]. Methods for assessing nutrition status include 24-h recall interviews, diet history (macro- and micronutrient intake), questionnaires (e.g. the Food Frequency Questionnaire and adherence scores), self-monitoring, medical exam, anthropometric measurements, body composition analysis, biochemical tests and assessments of physical function (e.g. grip test) [63,102,107].

6.3. Lifestyle counselling

6.3.1. Dietary/nutrition advice

Any nutrition interventions that are implemented following the assessment should be patient centric and individualized, taking into consideration the individual's personal values, food preferences and any social determinants of eating habits [27]. Nutrition advice has traditionally focused on a reduction in calorie intake to promote weight reduction; however, the increase in satiety typically experienced by patients taking a GLP-1 based therapy usually achieves the required calorie deficit for weight reduction. As a consequence there has been a shift from inducing weight reduction (through calorie restriction) to supporting patients in the adoption of dietary and activity patterns that will support optimal changes in body composition and general health and well-being [108]. Less focus is placed on the number of calories and more on the quality of the calories consumed.

Nutrition dietary advice should focus on the consumption of adequate protein (minimum of 0.8 g protein/kg bodyweight/day or 60–75 g/day), dietary fiber (21–25 g/day for women and 30–38 g/day for men or 14g/1000 kcal) and micronutrient intake, with multivitamin/mineral supplements considered if necessary [48,63,101]. After meeting protein needs, the balance of calories should come from nutrient-dense foods, that are low-fat and sources of complex carbohydrates. Maintaining adequate hydration during treatment with obesity medication is essential for the maintenance of renal function and should be tailored to individual needs based on climate, health status and exercise. A target fluid intake of >2–3 L/day is recommended, with minimal to moderate intake only of alcohol, caffeine and carbonated drinks [48,63,101].

The use of more prescriptive meal plans such as meal replacements, especially during the first few months of treatment, has been shown to have a positive benefit in terms of weight reduction in patients with T2DM and should be considered alongside obesity medication where appropriate [109,110]. Meal replacements may be used in conjunction with food as a partial diet replacement or used to provide the sole source of dietary energy (total replacement) and can minimize or remove the need for patients to choose between other high-energy-dense foods that are of poor nutrition quality [111].

Nutrition dietary advice should also encompass optimal eating patterns including providing guidance on maintaining a regular eating schedule, adopting planned portions sizes and ensuring the quality of food intake (Fig. 4) [48,101]. The reduced desire for food (i.e. fewer food cravings), or "dampening of food noise" often experienced by patients on a GLP-1 based therapy can also create a window of opportunity to encourage healthy eating, enabling individuals to achieve higher quality nutrition intake in the long term [101].

Fig. 4.

Strategies to promote successful nutrition and lifestyle management among people with obesity treated with obesity medications.

There are a number of healthy eating patterns that can serve as the foundation for dietary advice (e.g., Mediterranean, DASH [Dietary Approaches to Stop Hypertension], and plant-based diets). When providing nutrition dietary advice, it should be tailored to the individual taking into account food preferences (including cultural/ethnic preferences), lifestyle, socioeconomic level, (e.g. home environment, budget and food availability), other comorbidities with dietary implications (e.g. type 1 or 2 diabetes, cardiovascular disease, eating disorders, inflammatory bowel disease, non-alcoholic fatty liver disease) and any food restrictions (e.g. due to allergies, neurodiversity, sensory problems or coeliac disease) [98,99,102,112].

6.3.2. Physical activity

In addition to aiding the preservation of muscle mass and function in patients undergoing significant weight reduction, physical activity also offers health benefits independent of weight [113]. In a systematic literature review of the evidence for exercise in the management of overweight and obesity, a group of European experts concluded that there was a high level of evidence in support of a beneficial effect of exercise training programs on cardiometabolic health, including insulin sensitivity, systolic and diastolic blood pressure and intrahepatic fat [83]. In contrast, the benefits of aerobic exercise as a means of promoting weight reduction were considered to be minimal with an expected weight reduction of no more than 2–3 kg [83]. However, the addition of supervised exercise to GLP-1 based therapy has been shown to improve healthy weight maintenance after treatment is stopped compared with GLP-1 based therapy alone. In a post-treatment analysis of a randomized, placebo-controlled trial, weight reduction was better preserved 1 year after termination of treatment with a combination of once daily liraglutide plus supervised exercise compared with liraglutide alone for 1 year, with more patients who had previously received liraglutide combined with exercise maintaining a weight reduction of at least 10 % of initial body weight after treatment cessation (odds ratio versus liraglutide alone: 4.2 [95 % CI: 1.6, 10.8]) [114].

The topic of physical activity and exercise should be discussed during meetings between healthcare professional and patients with obesity, with patients encouraged to engage in physical activity, aerobic and resistance training, building up slowly and focusing on what is practical with agreed goals [115,116]. According to the WHO, a minimum of 150 min per week of moderate-intensity physical activity and resistance exercise training two or more times per week is recommended for adults aged 18–64 years including those with chronic conditions and those living with a disability. For older adults (aged ≥65 years), the WHO recommends varied multicomponent physical activity, with a focus on balance and strength training, of at least moderate intensity on three or more days each week [115]. As recommended by the Obesity Medicine Association (OMA), incorporating daily steps of 5000 to over 10,000 per day can often be an optional or complementary goal to the 150–300 min or more of moderate-intensity aerobic activity per week [81]. Physical activity may be part of everyday life (e.g. brisk walking, gardening or cycling) or part of supervised exercise programs, and should take into account the person's current physical fitness and ability for all activities. In addition, individuals should be encouraged to reduce sedentary behaviors (for example, screen-based leisure activities). Achieving greater than the recommended level of physical activity can help to mitigate the detrimental effects of high levels of sedentary behaviors [115].

6.3.3. Sleep hygiene

Poor sleep habits can significantly impact sleep duration, sleep quality and sleep timing and have been associated with metabolic disruption, reduction in physical activity, increased energy intake, and poor diet quality and eating behaviors, leading to an increased risk of obesity [117]. Education on the importance of good sleep hygiene should be provided as part of lifestyle counselling to patients on GLP-1 based therapy. Patients should be encouraged to adopt good sleep hygiene by establishing a consistent sleep schedule, creating a relaxing bedtime routine and avoiding screen time before bed, all of which can have a positive impact on weight management and weight reduction.

6.3.4. Mental health support

Mental health among patients with obesity can be significantly harmed due to weight bias and weight-based social stigma. Both internalized weight bias, whereby a patient engages in self-blame because of their weight, and stigma can lead to an increased risk of depression, anxiety, low self-esteem, social isolation, disordered eating patterns and avoidance of physical activity [118]. These negative feelings may also be further exacerbated by discrimination in the workplace and in educational and workplace settings. According to the Joint international consensus statement for ending the stigma of obesity, weight-based discrimination is one of the most common forms of discrimination in modern societies, with a prevalence of 19–42 % among patients with obesity, with higher rates among individuals with higher BMI and among women versus men [118].

Notably, stigma and an ambivalent attitude towards people with obesity and their management is not only present in society in general but has also been reported among some healthcare providers. In a Swedish survey of 235 primary care physicians, 47 % believed that one of the causes of obesity was lack of self-control, 22 % stated laziness as a cause and 14 % responded that individuals with obesity lack motivation to lose weight. Although almost all respondents (97 %) believed physicians could help patients with obesity, 87 % thought that losing weight was primarily the patient's responsibility [96]. Reframing obesity as a chronic medical condition instead of as a behavioral failure can help lessen internalized weight bias and stigma [119]. This reframed narrative is endorsed by the WHO [1] and is reflected in the 2025 global commission publication on the definition and diagnostic criteria of clinical obesity [4].

Importantly, support for mental health for patients with obesity receiving a GLP-1 based therapy should integrate conversations with the patient about obesity as a chronic disease and include discussion on changes in body image, changes in relationships, including with family, friends and the environment, and unrealistic expectations of treatment. Patients should also be monitored for eating disorders if necessary to ensure they are maintaining a healthy relationship with food, and referred to a behavioral health professional where appropriate [101,120].

6.4. Increasing medication adherence and persistence

Ensuring optimal medication adherence (i.e. that patients take their medication as prescribed) is fundamental to achieving the best outcomes for people taking obesity medications [25,121,122]; however, poor 1-year persistence and adherence has been reported among people with obesity receiving GLP-1 based therapy [123]. In a study evaluating pharmacy and medical claims data for 4066 commercially insured members with obesity without T2DM who newly initiated GLP-1 based therapy, 27.2 % (range 15.0–41.5 %) of patients were reported as adherent (defined as proportion of days covered >80 %) over a 1-year period [123]. Furthermore, data from two retrospective cohort studies reported a positive association with achieving at least 10 % weight reduction at 1 year and non-discontinuation of GLP-1 based therapy or late discontinuation (i.e. within 3–12 months of treatment initiation versus early discontinuation i.e. within 3 months of treatment initiation) [25,121].

The determinants of poor medication adherence in general are multifactorial and too numerous to discuss in detail in this review but can be broadly divided into five main categories which include patient-, healthcare team/system-, socioeconomic-, condition- and treatment-related factors [124]. The following section focuses on drug administration, side effects and drug access and costs in relation to adherence to GLP-1 based therapies.

6.4.1. Administration

Although some GLP-1 based therapies are available as single-use, pre-measured subcutaneous pens for ease of use, education of patients on correct administration technique remains important as many patients may not have previously self-administered a medication subcutaneously [Fig. 5] [101,125]. To ensure attainment of the optimal therapeutic effect from a GLP-1 based therapy, it is good practice to review patients to check their adherence, injection technique and injection sites [101,125]. A pharmacist or other healthcare professional should educate the patient on how to use the administration device, manage dose titrations and address missed doses [126]. As part of ongoing patient assessment, healthcare providers should also ensure their patient is being treated with the optimum dose that achieves the best balance between efficacy, tolerability and acceptability [125].

Fig. 5.

Practical approaches to improve adherence to obesity medications: addressing drug administration and side effects.

6.4.2. Side effects

GLP-1 based therapies are commonly associated with GI adverse events which may affect medication adherence and ultimately lead to patients discontinuing their treatment. In a systematic literature review of randomized controlled trials of GLP-1 based therapy in patients with obesity without T2DM, adverse events were reported in 80–96 % of patients treated with liraglutide or semaglutide compared with 63–96 % of placebo-treated patients; GI adverse effects were most commonly reported, occurring in 47–84 % (liraglutide/semaglutide) and 13–63 % (placebo) of patients [38]. In a second systematic literature review involving more than 400,000 patients with obesity and/or T2DM treated with liraglutide, semaglutide or tirzepatide, GI adverse events were again the most common with placebo-adjusted incidence ranges of 5–43 % for nausea, -7–39 % for diarrhea, 2–31 % for constipation, 0–26 % for vomiting, and 2–20 % for abdominal pain [47]. In a third study estimating the prevalence of GLP-1 based therapy discontinuation among new users with T2DM or obesity, patients who had new GI adverse events at follow-up were reported to have a significantly higher odds of treatment discontinuation at 12 months compared with patients who did not have a new GI adverse event (odds ratio: 1.04; 95 % CI: 1.02–1.06; p < 0.001) [127].

To manage expectations, all patients should be educated on the possibility of side effects occurring when they initiate treatment with a GLP-1 based therapy, whilst also highlighting that most GI side effects are transient and manageable [Fig. 5] [27,47,99,128,129]. Patients should be encouraged to report any side effects promptly. Gradual dose-escalation is recommended when initiating most GLP-1 based therapies to help reduce GI side effects. Practical strategies that can be adopted by the patient to mitigate short-term or mild GI side effects if they occur include eating slowly, eating smaller portions of food, limiting high fat and spicy foods, staying well hydrated, moderating intake of alcohol and fizzy drinks, increasing fiber intake, increasing physical activity and keeping a food diary to identify any trigger foods [97]. If GI side effects persist or become more severe, dose escalation should be paused and a differential diagnosis performed to identify or rule out any underlying GI disorders. A lower dose of the GLP-1 based therapy may be considered if the patient is unable to tolerate the standard maintenance dose and if this approach is unsuccessful, switching to a different GLP-1 based therapy, if available, may be an option. Checks should also be made that the patient understands and is complying with the diet/lifestyle guidelines. Short-term symptomatic pharmacological treatment (e.g. anti-emetics) may be appropriate in a small number of patients but is not universally recommended [99,128,129]. It is also important to remember that although usually transient, GI side effects can affect a patient's nutrition, fluid intake and mental well-being, necessitating the provision of appropriate support for affected patients [99,101].

6.4.3. Access and cost

Restricted access and/or affordability/cost of treatment can present major barriers to the initiation and continued use of GLP-1 based therapy [127,130]. In a retrospective cohort study, cost, alongside adverse events, was the most common specific documented reason for patients with obesity without T2DM discontinuing GLP-1 based therapy within 365 days [130]. In a second study estimating the prevalence of GLP-1 based therapy discontinuation among new users with T2DM or obesity, each one percentage point increase in out-of-pocket costs per 30-day supply of GLP-1 based therapy at 12 months of follow-up was associated with an increased odds of discontinuation (odds ratio: 1.02; 95 % CI: 1.02–1.03; p < 0.001) [127].

The cost of GLP-1 based therapy for weight management varies across different countries but is high for both patients and the healthcare system; insurance coverage for GLP-1 based drug treatment is available in a few high-income countries such as the US [131]. Alongside losing the health benefits of obesity medications, patients with obesity who experience non-medical discontinuation of their treatment often experience feelings of stigmatization, hopelessness and fear, and anger relating to the perceived injustice of have their treatment stopped [132]. Country- and pharma-led policy solutions, which are outside the scope of this review, are needed to address the current inequities in GLP-1 based therapy access and costs.

6.4.4. Other factors

An often-unrecognized contributor to the lack of adherence to GLP-1 based therapies is a less well defined, but in some patients, a more important factor, which is discontinuation of treatment for reasons unrelated to side effects or cost. A useful analogy is the earlier development of statins for the management of dyslipidemia. There are numerous large scale clinical trials that support the safety of statins and provide evidence of their beneficial effect on health outcomes [133]. Additionally, most statins are available as generic formulations, and even when administered at the highest dose often only cost a few dollars per month [134]; however, available data suggest that statin adherence may be only ∼50 % after one year [135]. It is possible that despite the clinical evidence, many patients remain unconvinced that statins are safe and effective or may be unable to afford the few dollars per month for generic statins; however, it is also conceivable that some patients may discontinue their statin therapy due to ‘drug fatigue’ (i.e. a reduced desire and motivation to adhere to their treatment) arising from chronic drug treatment and polypharmacy [136]. Similarly, long term adherence and persistence of GLP-1 based therapy for weight management may be impacted by drug fatigue and patients may also experience intrapersonal conflict, blaming themselves for their obesity and attributing their disease to a perceived lack of willpower that does not justify drug treatment [118,137,138].

6.5. Role of guidelines

Published nutrition guidelines specifically for medical patients receiving GLP-1 based therapy were not available prior to or during the specific time period covered in our literature search (February 2020 to February 2025), although published nutrition guidelines for patients who have undergone bariatric surgery were available [98,139,140]. Following completion of our literature search, a joint statement from the American College of Lifestyle Medicine, the American Society for Nutrition, the OMA, and the Obesity Society was published in May 2025 focusing on nutrition priorities to support GLP-1 based therapy for obesity [27]. This publication focuses in detail on eight key nutrition priorities including a patient-centered approach, nutrition assessment and screening, management of GI side effects, navigation of dietary preferences and intake, prevention of micronutrient deficiencies, preservation of muscle and bone mass, maximization of weight reduction and support for lifestyle changes.

The published nutrition guidelines for patients who have undergone bariatric surgery can also be applied to medical patients on obesity medications, as from a weight reduction perspective the GLP-1 based therapies achieve a similar weight outcome to bariatric surgery [98,139,140]. Other broader guidelines identified (i.e. not specific to GLP-1 based therapies) include the OMA clinical practice statement on nutrition and physical activity in patients with obesity [81] and the published expert opinion recommendations for nutrition assessment, management, and monitoring of patients treated with obesity medications [63]. Key points covered in these guidelines include patient evaluation and follow-up by a registered dietitian, recommendations for protein and fiber intake, hydration, supplemental vitamins and micronutrients. The guidelines also emphasize the need to assess nutrient deficiency risk factors, nutrient intake and body composition and to perform a nutrition-focused history and physical exam [63,81,98,139,140].

Alongside these recommendations for nutrition assessment, management, and monitoring, the Canadian Clinical Practice Guidelines for the Management of Obesity advocate for the use of a 5-step communication strategy between healthcare providers and people with obesity [Fig. 5] [84]. This 5-step counselling framework includes asking patient permission to talk about obesity, appropriate patient assessment, discussion of the core treatment options, reciprocal agreement of treatment goals and patient engagement in continued follow-up and reassessment [84,141]. More recently, the addition of a sixth strategy, based on an expert panel consensus, has been suggested and includes helping patients to find the resources they need to optimize their treatment outcomes [141].

7. Summary and concluding points

Healthcare providers face a number of major challenges to delivering optimal nutrition management to people with obesity treated with GLP-1 based therapy including the impact of obesity and weight reduction on body composition, particularly in terms of loss of muscle mass, the potential risk of sarcopenic obesity, and the problem of unhealthy nutrition.

Key takeaway clinical messages:

• •With the close support of dietitians, physicians should ensure that patients with suboptimal dietary patterns are identified and provided with timely and appropriate nutrition advice which focuses on the importance of adequate macronutrient, micronutrient and fluid intake, with particular emphasis on increased protein intake in conjunction with resistance training for the preservation of muscle mass.
• •Nutrition advice should be provided alongside other aspects of lifestyle counselling including support for mental health, sleep hygiene, physical activity and medication adherence and persistence.
• •Healthcare providers should also follow evidence-based nutrition guidelines where appropriate and ensure that any intervention is patient-centered and aligns with the needs and preferences of the individual.

CRediT author statement

Conceptualization, AF, LG, HEB; Writing—review and editing, AF, LG, HEB. All authors have read and agreed to the published version of the manuscript.

Declaration of Artificial Intelligence (AI) and AI-assisted technologies in the writing process

During the preparation of this work the authors did not use AI-assisted technologies.

Source of funding

This study was funded by Nestlé Health Science, Lausanne, Switzerland.

Declaration of competing interests

Dr Angela Fitch has served on advisory boards for Vivus, Currax, Eli Lilly, Novo Nordisk, Sidekick Health, Seca, and is a speaker for Eli Lilly, Novo Nordisk and Rhythm Pharmaceuticals. Linda Gigliotti has served on an expert panel on GLP-1 and nutrition for Nestlé Health Science and as a consultant for Amgen. Dr. Harold Bays’ research site institution has received research grants from 89Bio, Abbvie, Allergan, Alon Medtech/Epitomee, Aligos, Altimmune, Amgen, Anji Pharma, AstraZeneca, Bioage, Biohaven, Bionime, Boehringer Ingelheim, Carmot, Chorus/Bioage, Eli Lilly, Esperion, Evidera, Fractyl, GlaxoSmithKline, Graviton, HighTide, Home Access, Horizon, Ionis, Kallyope, LG-Chem, Marea, Madrigal, Merck, Mineralys, New Amsterdam, Novartis, NovoNordisk, Pfizer, Regeneron, Satsuma, Selecta, Shionogi, Skye/Birdrock, TIMI, Veru, Viking, Vivus, Zomagen. Dr. Harold Bays has served as a consultant (e.g., executive/national committee member, protocol/drug development advisor, and/or expert panel) for 89Bio, Altimmune, Amgen, Boehringer Ingelheim, Eva Pharma, Kiniksa, HighTide, Lilly, Nestle, Novo Nordisk, Regeneron, Rivus, Veru, Zomagen, ZyVersa.