Education programmes for people with chronic kidney disease and diabetes

Abstract

Background

Adherence to complex regimens for people with chronic kidney disease (CKD) and diabetes is often poor. Interventions to enhance adherence require intensive education and behavioural counselling. However, whether the existing evidence is scientifically rigorous and can support recommendations for routine use of educational programmes in people with CKD and diabetes is still unknown. This is an update of a review first published in 2011.

Objectives

To evaluate the benefits and harms of education programmes for people with CKD and diabetes.

Search methods

We searched the Cochrane Kidney and Transplant Register of Studies up to 19 July 2024 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov.

Selection criteria

We included randomised controlled trials (RCTs) and quasi‐RCTs investigating the benefits and harms of educational programmes (information and behavioural instructions and advice given by a healthcare provider, who could be a nurse, pharmacist, educator, health professional, medical practitioner, or healthcare provider, through verbal, written, audio‐recording, or computer‐aided modalities) for people 18 years and older with CKD and diabetes.

Data collection and analysis

Two authors independently screened the literature, determined study eligibility, assessed quality, and extracted and entered data. We expressed dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI) and continuous data as mean difference (MD) with 95% CI. Data were pooled using the random‐effects model. The certainty of the evidence was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach.

Main results

Eight studies (13 reports, 840 randomised participants) were included. The overall risk of bias was low for objective outcomes and attrition bias, unclear for selection bias, reporting bias and other biases, and high for subjective outcomes.

Education programmes compared to routine care alone probably decrease glycated haemoglobin (HbA1c) (4 studies, 467 participants: MD ‐0.42%, 95% CI ‐0.53 to ‐0.31; moderate certainty evidence; 13.5 months follow‐up) and may decrease total cholesterol (179 participants: MD ‐0.35 mmol/L, 95% CI ‐0.63 to ‐00.07; low certainty evidence) and low‐density lipoprotein (LDL) cholesterol (179 participants: MD ‐0.40 mmol/L, 95% CI ‐0.65 to ‐0.14; low certainty evidence) at 18 months of follow‐up.

One study (83 participants) reported education programmes for people receiving dialysis who have diabetes may improve the diabetes knowledge of diagnosis, monitoring, hypoglycaemia, hyperglycaemia, medication with insulin, oral medication, personal health habits, diet, exercise, chronic complications, and living with diabetes and coping with stress (all low certainty evidence). There may be an improvement in the general knowledge of diabetes at the end of the intervention and at the end of the three‐month follow‐up (one study, 97 participants; low certainty evidence) in people with diabetes and moderately increased albuminuria (A2).

In participants with diabetes and moderately increased albuminuria (A2) (one study, 97 participants), education programmes may improve a participant’s beliefs in treatment effectiveness and total self‐efficacy at the end of five weeks compared to routine care (low certainty evidence). Self‐efficacy for in‐home blood glucose monitoring and beliefs in personal control may increase at the end of the three‐month follow‐up (low certainty evidence). There were no differences in other self‐efficacy measures.

One study (100 participants) reported an education programme may increase change in behaviour for general diet, specific diet and home blood glucose monitoring at the end of treatment (low certainty evidence); however, at the end of three months of follow‐up, there may be no difference in any behaviour change outcomes (all low certainty evidence). There were uncertain effects on death, serious hypoglycaemia, and kidney failure due to very low certainty evidence. No data was available for changes in kidney function (creatinine clearance, serum creatinine, doubling of serum creatinine or proteinuria).

For an education programme plus multidisciplinary, co‐ordinated care compared to routine care, there may be little or no difference in HbA1c, kidney failure, estimated glomerular filtration rate (eGFR), systolic or diastolic blood pressure, hypoglycaemia, hyperglycaemia, and LDL and high‐density lipoprotein (HDL) cholesterol (all low certainty evidence in participants with type‐2 diabetes mellitus and documented advanced diabetic nephropathy). There were no data for death, patient‐orientated measures, change in kidney function (other than eGFR and albuminuria), cardiovascular disease morbidity, quality of life, or adverse events.

Authors' conclusions

Education programmes may improve knowledge of some areas related to diabetes care and some self‐management practices. Education programmes probably decrease HbA1c in people with CKD and diabetes, but the effect on other clinical outcomes is unclear. This review only included eight studies with small sample sizes. Therefore, more randomised studies are needed to examine the efficacy of education programmes on important clinical outcomes in people with CKD and diabetes.

Plain language summary

Do education programmes improve outcomes in people with both chronic kidney disease and diabetes?

Key messages

• For people with both chronic kidney disease (a long‐term condition where the kidneys do not work effectively) and diabetes (a lifelong condition that causes a person's blood sugar level to become too high), education programmes (planned activities designed to improve a person's ability to manage their condition) may improve their knowledge of diabetes, their ability to manage their condition, and self‐management behavioural changes.

• However, the small number of people enrolled in these studies and the wide range of outcomes reported means our findings must be interpreted cautiously. Larger, well‐designed studies with common outcomes and longer follow‐ups are needed.

Why is improving diabetes care important for people with kidney disease?

Chronic kidney disease (a long‐term condition where the kidneys do not work effectively) and diabetes (a lifelong condition that causes a person's blood sugar level to become too high) are chronic conditions that bring on many challenges for people, particularly when they have to manage both at the same time. Diabetes can accelerate the development of kidney disease and is the leading cause of kidney failure (a condition where the kidneys no longer function well enough to keep a person alive). While sticking to complex treatment plans can be challenging, successful self‐management in the early stages of kidney disease can improve outcomes later in life and delay the need for dialysis or a kidney transplant.

What are education programmes?

Education programmes are any set of planned activities designed to improve a person's ability to manage their condition and delay the progression of their kidney disease. These activities can aim to improve a person's knowledge of their disease, self‐care activities, and their ability to self‐monitor the disease, thus encouraging and motivating them to create healthy lifestyle changes, improve their treatment compliance, and improve quality of life.

What did we want to find out?

We wanted to find out whether an education programme designed for people with both kidney disease and diabetes helps them understand their condition and recognise the importance of strategies aimed at slowing its progression and preventing long‐term complications.

What did we do?

We searched for randomised studies (studies in which participants are assigned randomly to two or more treatment groups) that compared education programmes to usual care for people with both kidney disease and diabetes. We compared and summarised the results and rated our confidence in the evidence based on factors such as study methods and sizes.

What did we find?

We included eight studies involving 840 people 18 years or older with both kidney disease and diabetes. Four studies were undertaken in multiple centres, and four studies were performed in single centres. The duration of follow‐up ranged from 12 weeks to four years. Most of the education programmes were designed to increase a person's knowledge of their condition and improve self‐management behaviours. One study focused on reducing stress using mindfulness (a person's ability to be aware of where they are and what they are doing), and it was adapted to include practices for complex thoughts and feelings related to diabetes, and one study used a co‐ordinated medical care approach with multiple practitioners involved in a person's care.

Overall, education programmes probably lower blood glucose levels and may lower total cholesterol and blood pressure, but may make little or no difference to kidney function, abnormally low or high blood sugar, and cardiovascular disease (disorders of the heart and blood vessels).

For people with diabetes on dialysis (a procedure to remove waste products and excess fluid from the blood when the kidneys stop working properly), an education programme may improve their knowledge of diabetes, self‐management behaviour for checking their feet, using lotion, wearing appropriate shoes and socks, and coping with stress.

For people with moderately increased protein in the urine, there may be an improvement in their general knowledge of diabetes, their confidence in monitoring their blood sugar levels at home, their beliefs in their personal control, as well as behavioural changes to their diet. There may be no behavioural changes to exercise, foot care, or quitting smoking.

What are the limitations of the evidence?

We have low confidence in education programmes improving the understanding of diabetes in people with kidney disease. This is because the number of studies reporting outcomes of interest was low, and the education programmes varied, so we were unable to properly analyse the results.

How up‐to‐date is the evidence?

The evidence is current to July 2024.

Summary of findings

Summary of findings 1. Education programmes plus routine care versus routine care alone for people with chronic kidney disease and diabetes.

Education programmes plus routine care versus routine care alone for people with CKD and diabetes
Patient or population: people with CKD and diabetes Settings: multiple settings Intervention: education programmes plus routine care Comparator: routine care alone
Outcomes	Illustrative comparative risks* (95% CI)		Relative effect 95% CI	No. of participants (RCTs)	Quality of the evidence (GRADE)
	Assumed risk	Corresponding risk
	Routine care alone	Education programmes plus routine care
All‐cause death Follow‐up: 9 months	41 per 1000	34 per 1000 (13 to 91)	0.83 (0.31 to 2.19)	424 (4)	⊕ ⊕ ⊖ ⊖ LOW 1,2
Serious hypoglycaemia Follow‐up: 18 months	67 per 1000	5 per 1000 (0 to 90)	0.08 (0.0 to 1.33)	179 (1)	⊕ ⊕ ⊖ ⊖ LOW 1,3
HbA1c (%) Mean follow‐up: 13.5 months	The mean HbA1c was 0.42% lower with education programmes plus routine care (0.53% lower to 0.31% lower) compared to routine care alone		‐	467 (4)	⊕ ⊕ ⊖ ⊖ MODERATE 1
Behaviour change: home blood glucose monitoring (SDSCA) (higher score better) Follow‐up: immediately post‐intervention	The mean change in home blood glucose monitoring score was 2.13 higher with education programmes plus routine care (1.18 higher to 3.08 higher) compared to routine care alone		‐	100 (1)	⊕ ⊕ ⊖ ⊖ LOW 1,3
Behaviour change: home blood glucose monitoring (SDSCA) (higher score better) Follow‐up: 3 months	The mean change in home blood glucose monitoring score was 11.28 higher with education programmes plus routine care (1.92 higher to 20.64 higher) compared to routine care alone		‐	79 (1)	⊕ ⊖ ⊖ ⊖ VERY LOW 3,4
Quality of life: PHQ stress score (lower score better) Follow‐up: 12 months	The mean PHQ stress score was ‐1.70 lower with education programmes plus routine care (‐3.09 lower to ‐0.31 lower) compared to routine care alone		‐	103 (1)	⊕ ⊖ ⊖ ⊖ VERY LOW3,4
General knowledge of diabetes (ADDQoL) (higher score better) Follow‐up: 3 months	The mean ADDQoL general knowledge score was 14.39 higher with education programmes plus routine care (7.45 higher to 21.33 higher) compared to routine care alone		‐	97 (1)	⊕ ⊕ ⊖ ⊖ LOW 1,3
Self‐efficacy at the end of education intervention (ADDQoL) (higher score better) Follow‐up: 5 weeks	The mean ADDQoL self‐efficacy total score was 19.00 higher with education programmes plus routine care (12.58 higher to 25.42 higher) compared to routine care alone		‐	97 (1)	⊕ ⊕ ⊖ ⊖ LOW1,3
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). ADDQoL: Audit of Diabetes Dependent Quality of Life; CI: Confidence interval; CKD: Chronic kidney disease; MD: Mean difference; PHQ: Patient Health Questionnaire; RR: Risk ratio; SDSCA: Summary of Diabetes Self‐Care Activities
GRADE Working User Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

¹ Due to serious risk of bias

² Due to serious imprecision (due to low events)

³ Due to serious imprecision

⁴ Due to very serious risk of bias

Background

Description of the condition

Chronic kidney disease (CKD) is a global health problem affecting 5% to 10% of the global population, contributing to over 1.1 million deaths worldwide in 2015 (GBD 2015; KDIGO 2009). Diabetes mellitus (DM) can accelerate CKD development, and it is recognised as the leading cause of kidney failure and results in a poorer prognosis for patients (AIHW 2024; Chantrel 1999; Kasper 2005; KDOQI 2007; KDOQI 2012; KHA 2010; Narres 2016; Shen 2016; Toto 2002; USRDS 1998; USRDS 2005; USRDS 2009). Diabetic kidney disease (DKD) is a progressive disease revealed by clinical assessment, including measurement of albuminuria, reduced glomerular filtration rate (GFR), or both. Patients ordinarily have the presence of severely elevated albuminuria > 300 mg/24 hours (or > 200 μg/min) or a urinary albumin‐creatinine ratio (UACR) > 300 mg/g (confirmed in at least two of three samples), as well as diabetic retinopathy and the absence of signs of other forms of kidney disease. Patients will usually have raised blood pressure (BP) and more significant cardiovascular morbidity and death (De Boer 2011; Persson 2018). More than 90% of people with DM have type 2 diabetes (T2DM), and the annual growth rate of DM‐related CKD is expected to grow dramatically due to an increase in people with T2DM. In 2020, within a primary care setting, the estimated prevalence of CKD stages 3 to 5 (eGFR < 60 mL/min/1.73 m²) in T2DM patients was estimated at 24.4% (95% confidence interval (CI) 21.9 to 27.0) (Jitraknatee 2020).

The clinical manifestations of DKD have changed over recent years, and the definition of DKD has expanded. Typically, the first clinical signs of DKD were an increase in urine albumin excretion, worsening to albuminuria, followed by a loss of GFR. In comparison, it is now not uncommon to see patients who have a steady decline in GFR without albuminuria (approximately 6% of DKD patients); this is possibly due to advancement in early detection and treatment (Afkarian 2016; Foley 2009; Gheith 2016; Selvin 2007; White 2014). Alarmingly, approximately 20% to 50% of T2DM patients and nearly half of patients with type 1 DM (T1DM) develop DKD throughout their lifetime, and National Health and Nutrition Examination Survey (NHANES) data found approximately 8.2 million adults with DM (95% CI 6.5 to 9.9 million adults) had albuminuria, reduced eGFR, or both from 2009 to 2014 (Afkarian 2016; Gheith 2016; Ritz 1999).

Recent evidence suggests that the overall prevalence of DKD has not significantly changed over time from 28.4% (95% CI 23.8% to 32.9%) between 1988 and 1994 to 26.2% (95% CI 22.6% to 29.9%) between 2009 and 2014 (prevalence ratio, 0.95, 95% CI 0.86 to 1.06; adjusting for age, sex, and race/ethnicity; P = 0.39 for trend). However, the population of existing patients whose kidney failure was caused by DM (tripled from 1990 to 2000) is expected to grow 10‐fold by 2030, to 1.3 million (Collins 2005). This significant burden will further stress already struggling healthcare systems worldwide (Aziz 2018). In the USA, DKD accounts for 50% of kidney failure, up from 18% in 1980 (De Boer 2011; KDOQI 2007). It is estimated that 10% of deaths in T2DM patients are attributable to kidney failure (van Dieren 2010). DM and CKD are common and are synergistically associated with premature death in the general population (Middleton 2006; Narres 2016; Shen 2016). The survival of patients with DKD decreases once kidney failure occurs and is estimated as low as 40% in five years (Shen 2016). Furthermore, data from studies conducted in the USA show a high economic burden associated; the medicare costs spent on the kidney failure programme were about 26.8 billion US dollars in 2008 (De Boer 2011; USRDS 2000; USRDS 2001).

Description of the intervention

People who are well‐equipped to self‐manage their condition are likely to be more empowered to make better health‐related decisions (Anekwe 2018; Chen 2016; Slama‐Chaudhry 2019). Education interventions can potentially reduce the economic burden and demand for health service provision (Chen 2016). These factors justify the intensive efforts needed to prevent CKD and DM progression through education to improve self‐management. The success of strategies to promote glycaemic control and minimise the progression of DKD depends on patients' ability and willingness to change and subsequently maintain appropriate lifestyle behaviours regarding diet, physical activity, adjusting to psychological and social demands, managing complex medication regimens, self‐monitoring, and engaging in effective interactions with health care providers and medical follow‐up visits (Anekwe 2018; Captieux 2018; Slama‐Chaudhry 2019). Adherence to complex regimens remains challenging, and a multifactorial treatment approach that includes patient education can support self‐management for people with both CKD and diabetes (Persson 2018). For this review's purpose, education programmes are defined as any set of planned educational activities designed to improve the person's ability to manage and delay the progression of their CKD.

How the intervention might work

Behaviour can be modified in many ways to minimise disease burden across all stages of DM and CKD. A well‐designed education programme is a vital resource to support behaviour change and may provide advice to help people make more informed health choices and adhere to recommended medical regimes (Aziz 2018; Kim 2019). Education interventions may improve knowledge of their disease and empower and motivate them to create healthy preventative strategies that ultimately slow the progression of CKD and DM.

Other education interventions might be more hands‐on, involving training for self‐care activities or disease self‐monitoring. This may include the patient's caregivers or a multidisciplinary care team (Baig 2015; Shi 2016). For some people, having more responsibility for day‐to‐day disease management makes them feel more in control of their condition. It may improve their quality of life (QoL), emotional well‐being, and other DM and CKD outcomes (Windrum 2016). Similar interventions might be more directed at improving medication adherence. Patients with a good grasp of their condition have better compliance and satisfaction with their medical regimen and fewer missed appointments (Kaplan‐Lewis 2013).

The efficacy of educational programmes for those with DM has been studied comprehensively for several decades (ADA 2001; Boulton 1998; Calman 1994; Captieux 2018; Duke 2009; Hawthorne 2008; KDOQI 2007; Norris 2002; Pecoraro 1990). Several meta‐analyses and systematic reviews of education interventions have demonstrated that they are effective in producing positive patient outcomes in terms of glycaemic control, weight management, adherence to medications, and improvement of psychological well‐being and QoL in diverse socio‐economic and ethnic communities (Brown 1990; Captieux 2018; Dorresteijn 2014; Ellis 2004; Gary 2003; Norris 2002; Steed 2003). Similar findings have been found in systematic reviews in the general CKD population, with the addition of improvement in knowledge, self‐efficacy, lifestyle modification (exercise and diet), death, dialysis therapy initiation, and important clinical outcomes (serum albumin, proteinuria, and haemoglobin) (Lopez‐Vargas 2016; Persson 2018).

Overall, DM is primarily a self‐managed disease, and in turn, so is having both CKD and DM, particularly in the early stages of CKD progression (Windrum 2016). Given the complex nature of managing both CKD and DM concurrently, it is likely that interventions will need to be tailored to each patient's circumstances to meet the needs of patients with diverse ethnic, cultural, literacy, and geographical backgrounds, particularly when other co‐morbidities are taken into account. Other essential factors that must be considered include ethnic, cultural, literacy, cognitive, and geographical factors, as recognised in recent guidelines (KDIGO 2022). In many cases, patients will work together with several healthcare professionals, and the overall care plan for the patient is usually dynamic. The healthcare professionals may include a general practitioner, nephrologist, diabetes specialist, health care navigator, nurse‐educator, dietician, psychologist, podiatrist, family member or caregiver, and social worker. The type of education conveyed may also influence how effective the intervention is. Evidence from the DM population has suggested that having “patient‐centred education”, where self‐management plans are developed and maintained through a collaboration between patients and their health care providers, is more effective at improving glycaemic control, changing behaviours, and maintaining compliance compared to when the patient has little involvement (Windrum 2016). Background knowledge of both CKD and DM helps patients understand their disease and recognise the importance of strategies aimed at secondary and tertiary prevention of DKD, hyperglycaemia and hypertension.

Why it is important to do this review

Evidence suggests that educational programmes aimed at lifestyle modification might be effective in slowing down the progression of coexisting CKD and DM. Early intervention and advice to patients about regular screening and medical adherence are important to stop DM and CKD from accelerating and leading to kidney failure. There is the potential to reduce the risk of death and other clinical outcomes and improve the QoL. Whether the existing evidence is scientifically rigorous and can support recommendations for the routine use of educational programmes in coexisting CKD and DM is still unknown.

Objectives

To evaluate the benefits and harms of education programmes for people with both CKD and DM.

Methods

Criteria for considering studies for this review

Types of studies

All randomised controlled trials (RCTs) and quasi‐RCTs (in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at the benefits and harms of educational programmes for people with both CKD and DM were included. In randomised cross‐over studies, only the first period before cross‐over was included.

Types of participants

Inclusion criteria

People aged 18 years or over with both CKD and T1DM or T2DM, or DKD were included.

Definition of CKD

Participants with CKD stages G1 to G5 (people with G1 required moderately (A2) to severely (A3) increased albuminuria, including kidney replacement therapy (KRT) or transplant) as outlined in KDIGO 2022a.

Definition of DM

According to WHO criteria (WHO 1999), fasting plasma glucose ≥ 7.0 mmol/L and two‐hour plasma glucose ≥ 11.1 mmol/L.

Definition of DKD

DKD is defined by albuminuria (urinary albumin excretion (UAE) ≥ 3.4 mg/mmol (30 mg/g)) and progressive reduction in estimated (e)GFR in the setting of a long duration of diabetes (> 10 years' duration of T1DM diabetes; may be present at diagnosis in T2DM) and is typically associated with retinopathy.

Exclusion criteria

People with kidney damage due to DM other than T1DM or T2DM, such as gestational diabetes, were excluded.

Types of interventions

Any educational programme (or programmes that include education) used for people with both CKD and DM to prevent the progression of CKD, improve diabetic control, and improve QoL.

Educational programmes have to comprise information and behavioural instructions and advice given by a healthcare provider, who could be a nurse, pharmacist, educator, health professional, medical practitioner, or healthcare provider, through verbal, written, audio‐recording, or computer‐aided modalities.

The educational intervention could occur in the emergency department, hospital, the person's home, or in the community.

Interventions that included pharmacological therapies in the intervention arm alone were excluded. Standard care across both arms, including pharmacological interventions, was included.

The mode of delivery and reach of the intervention depended on the aim of the intervention, but all types were included in this review. Examples of delivery modes may include but were not limited to, face‐to‐face, over the phone, group sessions, computer, DVD, mobile application, or a mix.

Interventions that compare technology, such as medical device aids, were excluded.

Types of outcome measures

The time intervals at which outcome assessment takes place may affect the outcomes of educational programmes. If the data were available, we considered six months, one, and two years as standard time intervals.

Primary outcomes

1. Death: (including all causes of death; DKD‐related death (total and specific death rates from causes attributable to DKD); cardiovascular‐related death)

2. Glycated haemoglobin (HbA1c); attaining a HbA1c target

3. Kidney failure

4. Patient‐oriented measures of knowledge, self‐management, and behavioural changes: attitude scales; knowledge of DKD/DM; patient empowerment and self‐efficacy; patient behavioural changes (including smoking cessation, increased exercise, diet modification, and adherence to medications); any other self‐management measures.

Secondary outcomes

1. Kidney function measures during follow‐up: creatinine clearance, eGFR, serum creatinine (SCr), doubling SCr, proteinuria, and albuminuria

2. BP (changes in or mean): total, systolic (SBP), and diastolic (DBP)

3. Glycaemic events: hypoglycaemia, severe hypoglycaemia (measured as having low blood glucose levels that require assistance from another person to treat)

4. Cardiovascular (CV) morbidity (non‐fatal): total CV disease events (stroke, myocardial infarction (MI), heart failure, any other reported CV events); the incidence of peripheral heart disease

5. Measures of QoL (any scale); health‐related QoL (any scale)

6. Lipids: total cholesterol; low‐density lipoprotein (LDL); high‐density lipoprotein (HDL); triglycerides

7. Adverse events: any adverse events related to the educational programmes (e.g. deteriorating QoL or biomedical parameters).

Search methods for identification of studies

Electronic searches

We searched the Cochrane Kidney and Transplant Register of Studies up to 19 July 2024 through contact with the Information Specialist using search terms relevant to this review. The Register contains studies identified from the following sources:

1. Monthly searches the Cochrane Central Register of Controlled Trials (CENTRAL)

2. Weekly searches of MEDLINE OVID SP

3. Hand searching of kidney‐related journals and the proceedings of major kidney conferences

4. Searching the current year of EMBASE OVID SP

5. Weekly current awareness alerts for selected kidney and transplant journals

6. Searches of the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.

Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE based on Cochrane Kidney and Transplant's scope. Details of search strategies and a list of hand‐searched journals, conference proceedings and current awareness alerts are available in the Specialised Register section of information about Cochrane Kidney and Transplant.

See Appendix 1 for search terms used in strategies for this review.

Searching other resources

The previous version of the review (Li 2011) searched the following databases and resources for the initial review. Please note the databases listed below were not searched for this 2024 update.

1. Four Chinese medicine databases: CBM‐disc (1979 to December 2009), Chinese Science and Technique Journals Database (VIP) (until December 2009), China National Infrastructure (CNKI) (until December 2009) and the WanFang database (until December 2009)

2. Education Resources Information Centre (ERIC) (www.eric.ed.gov) (July 2010)

3. Campbell Collaboration's Social, Psychological, Educational and Criminological Trials Register (geb9101.gse.upenn.edu)

4. European Medicines Agency (EMEA) (www.emea.europa.eu/index/indexh1.htm) (July 2010).

The previous version of the review (Li 2011) and the 2024 update also sought information from the following.

1. Reference lists of review articles, relevant studies and clinical practice guidelines

2. Letters seeking information about unpublished or incomplete studies were sent to investigators known to be involved in previous studies.

Data collection and analysis

Selection of studies

The search strategy described was performed to identify eligible studies. Two authors (BC, TC) independently determined each study's eligibility, identified by the search, by reading the title, abstract, and, if necessary, the full text. Disagreements were resolved in consultation with a third author (DT). Studies and reviews that might include relevant data or information on studies were retained initially. The review authors then independently eliminated studies that did not satisfy the inclusion criteria and obtained full copies of the remaining studies.

Two review authors (BC, TC) independently read these reports to select relevant studies. We included studies regardless of whether measured outcome data were reported in a 'usable' way.

Where duplication reports of the same study were confirmed, the initial first complete publication (index publication) was selected. It was the primary data source, but additional prior or subsequent reports were also included. These other prior or subsequent reports containing supplementary outcome data (e.g. longer‐term follow‐up or different outcomes) also contributed to the meta‐analysis.

Data extraction and management

Two authors (BC, TC) independently extracted data using a standard form and checked for agreement before entry into Review Manager. Unclear data were clarified by contacting the author of the study report, and any relevant data obtained in this manner were included in the review.

We included information about the type of education intervention, the number of participants treated, the study design (standard of care or active control), the study duration and follow‐up, important kidney function, diabetic, cardiovascular, and QoL outcome measures and results, withdrawals, and adverse events.

We collected the studies' characteristics in sufficient detail to complete the table of the included studies' characteristics. In the event of disagreement, a third review author adjudicated (DT).

Assessment of risk of bias in included studies

The following items were assessed independently by two authors (BC, TC) using the risk of bias assessment tool (Higgins 2022) (seeAppendix 2).

• Was there adequate sequence generation (selection bias)?

• Was allocation adequately concealed (selection bias)?

• Was knowledge of the allocated interventions adequately prevented during the study?

  • Participants and personnel (performance bias)

  • Outcome assessors (detection bias)

• Was incomplete outcome data adequately addressed (attrition bias)?

• Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?

Measures of treatment effect

For dichotomous outcomes (e.g. incidence of all‐cause death, DKD‐related death, CV disease‐related death, incidence of kidney death during follow‐up, kidney failure, CV disease events, self‐management, behavioural change, adverse events), results were expressed as risk ratios (RR) with a 95% CI.

Where continuous scales of measurement were used to assess the effects of educational programmes (e.g. eGFR, SCr, albuminuria, UACR, proteinuria, BP, lipids, blood glucose, QoL, behaviour change), the mean difference (MD) was used, or the standardised mean difference (SMD) if different scales were used with 95% CI.

Unit of analysis issues

If non‐standard designs were found, such as cluster RCTs and cross‐over studies, then the analysis would have been conducted following the guidelines in the Cochrane Handbook to avoid unit‐of‐analysis errors (Higgins 2022).

Dealing with missing data

Any further information required from the original author was requested by correspondence, and any relevant information obtained in this manner was included in the review. Where a study reported outcome data after excluding some randomised participants from the denominator, further information required from the original author was requested by email, and any relevant information obtained in this manner was included in the review. Evaluation of important numerical data such as screened, randomised patients, as well as intention‐to‐treat (ITT), as‐treated and per‐protocol population, were carefully performed. Attrition rates, for example, drop‐outs, losses to follow‐up and withdrawals were investigated. Issues of missing data and imputation methods (e.g. the last observation carried forward) were critically appraised (Higgins 2022). We used a modified ITT analysis where the ITT population consisted of participants who were randomised, received at least one dose of the assigned study treatment and provided at least one post‐baseline assessment. We assigned missing participants zero improvements wherever possible.

Assessment of heterogeneity

We first assessed for statistical heterogeneity visually by inspecting forest plots of standardised mean effect sizes and risk ratios. Furthermore, we applied a Chi² test to assess heterogeneity. With P < 0.10 used to denote statistical significance and with I² calculated to measure the proportion of total variation in the estimates of treatment effect due to heterogeneity beyond chance (Higgins 2022), we used conventions of interpretation that were defined by Higgins 2003. However, the limited amount of study data published did not enable meaningful interpretation. We had also planned to conduct subgroup analysis and meta‐regression to evaluate potential sources of heterogeneity, but this was not possible because of the small number of studies of paired interventions.

Assessment of reporting biases

If sufficient RCTs were identified, an attempt was made to examine for publication bias using a funnel plot (Higgins 2022). We planned to assess publication bias using a method designed to detect the amount of unpublished data with a null effect required to make any result clinically irrelevant (usually taken to mean a number needed to treat (NNT) of 10 or higher) (Higgins 2022). Insufficient studies were identified to assess publication bias.

Data synthesis

Data were abstracted from individual studies and then pooled using random‐effects meta‐analysis. The random‐effects model was chosen because it provides a more conservative estimate of effect in the presence of known or unknown potential heterogeneity (Deeks 2001). The statistical method used was Mantel‐Henzel meta‐analysis for dichotomous data and generic inverse variance meta‐analysis for continuous data.

Subgroup analysis and investigation of heterogeneity

Subgroup analysis was to be used to explore possible sources of heterogeneity (e.g. participants, interventions and study quality). Heterogeneity amongst participants could be related to age, type of diabetes, and CKD (e.g. pre‐dialysis patients, patients on dialysis, and transplant patients). Heterogeneity in educational programme interventions could be related to educational content (e.g. BP programmes, diabetes programmes, weight control programmes), the healthcare providers, mode, and administration duration. Adverse effects were to be tabulated and assessed with descriptive techniques as they were likely different for the various educational programmes used. The risk difference (RD) with 95% CI was to be calculated for each adverse effect, compared with no administration of education programmes. There were insufficient studies identified to undertake subgroup analysis.

Sensitivity analysis

The following sensitivity analyses were considered.

• Repeating the analysis, excluding unpublished studies

• Repeating the analysis, taking account of the risk of bias, as specified

• Repeating the analysis, excluding any very long or large studies to establish how much they dominate the results

• Repeating the analysis excluding studies using the following filters: language of publication, source of funding (industry versus other), and country the study was conducted in.

However, insufficient data were available to determine the influence of the effect size.

Summary of findings and assessment of the certainty of the evidence

We have presented the main results of the review in the summary of findings tables. These tables present key information concerning the quality of the evidence, the magnitude of the effects of the interventions examined, and the sum of the available data for the main outcomes (Schünemann 2022a). The summary of findings tables also include an overall grading of the evidence related to each of the main outcomes using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach (GRADE 2008; GRADE 2011). The GRADE approach defines the certainty of the evidence as to the extent to which one can be confident that an estimate of effect or association is close to the true quantity of specific interest. The quality of a body of evidence involves considering the within‐trial risk of bias (methodological quality), the directness of evidence, heterogeneity, the precision of effect estimates, and publication bias (Schünemann 2022b).

In the summary of findings table for the comparison of an education programme plus routine care versus routine care, we presented the following outcomes.

• Death (all causes)

• Glycaemic events: serious hypoglycaemia

• HbA1c (%)

• Behaviour change at the end of treatment (five weeks): home blood glucose monitoring (HBGM)

• Behaviour change at three months follow‐up: home blood glucose monitoring

• QoL: Patient Health Questionnaire (PHQ) stress score

• Self‐efficacy at the end of education intervention

• General knowledge of diabetes at the end of education intervention

No summary of findings tables were presented for other comparisons due to insufficient data.

Results

Description of studies

The following section contains broad descriptions of the studies considered in this review. For further details on each individual study, please see Characteristics of excluded studies; Characteristics of included studies; Characteristics of ongoing studies; Characteristics of studies awaiting classification.

Results of the search

For this update, we searched the Cochrane Kidney and Transplant Register of Studies (up to 19 July 2024) and identified 177 reports. Five new studies (nine reports) were included, 37 studies (55 reports) were excluded, and one ongoing study (one report) was identified. One new study is awaiting classification (recently completed; no data available). We also identified 110 new reports of existing excluded studies.

We reassessed and reclassified one excluded study as an included study (Fogelfeld 2017), and one ongoing study has now been completed and moved to Studies awaiting classification as no data have been published (NCT00782847). Finally, eight excluded studies have been deleted (not randomised, wrong population or intervention).

Eight studies were included (13 reports, 840 randomised participants), 59 were excluded, two are awaiting classification, and one study is ongoing (Figure 1).

1.

Flow chart showing study selection

Included studies

Eight studies were included (13 reports, 840 randomised participants) (C‐DIRECT 2019; Fogelfeld 2017; Guo 2022; Kopf 2012; McMurray 2002; MEMO 2011; MESMI 2010; Steed 2005).

See Characteristics of included studies.

All studies enrolled adults. C‐DIRECT 2019 reported participants older than 21 years, Fogelfeld 2017 included participants between 18 and 70 years, Kopf 2012 included participants between 30 and 70 years, MESMI 2010 included participants > 18 years, and Steed 2005 included adults < 70 years of age. Guo 2022, McMurray 2002, and MEMO 2011 did not report the age range.

C‐DIRECT 2019, McMurray 2002, MEMO 2011 and Steed 2005 were multicentre studies, while the remaining were single‐centre studies.

There was some variation between the type of DM, albuminuria and CKD stage included in the studies. All studies included T2DM participants, while McMurray 2002 and MESMI 2010 also included participants with T1DM. MEMO 2011 included participants with moderately increased albuminuria or overt proteinuria with a SCr < 180 µmol/L. Fogelfeld 2017 included participants with a documented advanced diabetic nephropathy defined as impaired kidney function (eGFR calculated by the Modified Diet in Renal Disease (MDRD) equation) corresponding to CKD stages 3 to 4 (moderate‐severe, i.e. eGFR > 15 and < 60 mL/min) and presence of proteinuria or albuminuria as follows:

• The current presence of severely increased albuminuria (A3)

• The current presence of moderately increased albuminuria (A2) and documentation of previous severely increased albuminuria (A3)

• The current presence of moderately increased albuminuria (A2) and documentation of diabetic retinopathy or laser therapy

• If only moderately increased albuminuria (A2) and A, B, or C criteria are not fulfilled, then renal ultrasound should be done to demonstrate normal‐sized kidneys.

Participants from Kopf 2012 had albuminuria (> 20 mg/L in two separate spot urines) and a documented history of moderate albuminuria (A2) in at least two separate urine samples (UAE > 30 mg/24 hours or > 20 mg/L). In addition to having DM, McMurray 2002 included participants with kidney failure who required KRT with either haemodialysis (HD) or peritoneal dialysis (PD) for more than 30 months. Steed 2005 included participants with moderately increased albuminuria (A2) (indicated by two or more UACR > 3.0 mg/mmol or 24 hours UAE > 30 mg/24 h) and stage 3 DKD. MESMI 2010 included participants with an eGFR > 15 and < 60 mL/min/ 1.73 m² or DKD (moderately increased UACR > 2.0 mg/mmol for men, > 3.5 mg/mmol for women) and systolic hypertension >130 mm Hg treated with prescribed antihypertensive medication. Finally, Guo 2022 included DKD participants who met the diagnostic criteria of DKD in the uraemic phase.

Interventions and comparisons

C‐DIRECT 2019, MESMI 2010, MEMO 2011, Fogelfeld 2017 and Guo 2022 were described in the text as multifactorial interventions focusing on improving self‐management. In addition to being multifactorial, Fogelfeld 2017 and Guo 2022 used a co‐ordinated medical care approach. Multiple practitioners from various disciplines were present at the participants' appointments and shared the decision‐making for their treatments. For this reason, this comparison was analysed separately. The Fogelfeld 2017 and Guo 2022 comparison was "Multidisciplinary, multifactorial education programmes versus routine care". The C‐DIRECT 2019 intervention delivered education sessions at the bedside while participants underwent HD and were delivered by nurses, typically taking 30 to 60 minutes. The intervention was modelled on the (HED‐SMART) renal programme (Griva 2018). However, its context and delivery were tailored to the needs and context of co‐existing DM and kidney failure, as identified in a previous mixed methods study (Griva 2011; Griva 2015).

In MESMI 2010, the participants received standard care offered to participants with both CKD and DM attending diabetes and nephrology outpatient clinics at the hospital. BP control was the most important aspect of routine care, and treatment was provided depending on the patient’s circumstances and morbidity. Data were collected from the control group at the same time as the intervention group. The multifactorial intervention consisted of the following:

• Self‐monitoring of BP, individualised medication review, 20‐minute DVD, and fortnightly motivational interviewing follow‐up telephone contact for 12 weeks (to support BP control and optimal medication self‐management).

• Delivered by an intervention nurse with a kidney specialist and doctoral qualifications and trained in motivational interviewing using a checklist and standing script for fidelity purposes.

• Participants in the intervention group were taught how to take their BP, which involved sitting every morning after breakfast and taking their medications using their non‐dominant arm with an A&D Medical Pty. Ltd. A digital BP monitor (Model UA‐787, Saitama, Japan), which was supplied for the study.

• Participants recorded their daily BP for approximately three months in a specific booklet issued for this purpose. The individualised medication review involved the intervention nurse drawing up a chart of the participant’s prescribed medications, including the drug's generic name, what the medication was for, the dose and when to take it, and targets for which to aim.

• The 20‐minute DVD involved an interactive, psychosocial approach to motivating people to take medication, appealing to knowledge, thoughts and feelings underpinned by the modified Health Belief Model.

In MEMO 2011, both treatment groups received a similar routine of care by their own clinician according to local guidelines, consistent with the National Institute of Clinical Excellence (NICE) guidance on managing individuals with T2DM and DKD. It also provides additional information on managing individuals with T2DM of South Asian ethnicity. Participants in the control group were not seen or treated by the study physician or team and had usual access to education provided as part of standard diabetes care in either primary or secondary care. Like MESMI 2010, the intervention focused on self‐monitoring and followed up on goal setting for medical adherence and lifestyle changes during individual three‐month visits. The participants discussed and recorded lifestyle changes and medication adherence in record books, including general information on DM. It is unclear how or if these differed between the groups.

Kopf 2012 was the only mindfulness‐based stress reduction education intervention study. It was adapted to include practices for complex thoughts and feelings related to DM. It consisted of an eight‐week programme based on body and meditation practices to increase openness, awareness and acceptance of all internal and external experiences. A psychologist and a resident in internal medicine led this.

McMurray 2002 and Steed 2005 also focused on improving self‐management through education, diabetes care monitoring, and management, and both were led face‐to‐face by a diabetes specialist and dietician. To guarantee standardised medical treatment as usual according to diabetes guidelines in both arms, all participants were seen regularly by a physician in the outpatient clinic.

The routine treatment group for McMurray 2002 included diet control, glycaemic control (e.g. insulin injection), antihypertensive drugs, and HD or PD therapy. The diabetes care manager provided the education and care management programme for the participants in the treatment group, which lasted for 12 months.

In Steed 2005, the routine treatment group received no additional education or attention other than completing assessments and receiving 'routine treatment' (not reported in detail).

Excluded studies

Fifty‐nine studies were excluded. The reasons for exclusion were:

• Wrong population (42 studies)

• Wrong intervention (16 studies)

• Study retracted (one study).

See Characteristics of excluded studies.

Ongoing studies

One ongoing study (NCT03413215) plans to compare additional counselling and education by a diabetes nurse educator and medical social worker over 12 months with standard care.

See Characteristics of ongoing studies.

Studies awaiting classification

Two studies (NCT00782847; Suvamat 2023) have been completed and are awaiting classification, as there are currently no published results.

• NCT00782847 compared the DiaNE consultation and support programme given over four weeks with standard care.

• Suvamat 2023 compared face‐to‐face group activities with motivational interviews with usual care.

Risk of bias in included studies

Figure 2 summarises the risks of bias for the studies overall, and Figure 3 reports the risks of bias in each individual study.

2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Allocation

Random sequence generation

One study was judged to be a high risk of bias for random sequence generation (McMurray 2002) due to an inadequate randomisation method. The HD participants were randomised to the treatment or control groups according to the date of undergoing HD therapy (patients who underwent HD on Monday, Wednesday and Friday were assigned to the study group; Tuesday, Thursday and Saturday patients were assigned to the control group). Insufficient detail was reported for PD patients, and patients were deemed "numerically randomised". No details of the randomisation sequence were provided.

Five studies were judged to have an unclear risk of bias. The studies were described as RCTs and reports randomly assigning participants to one of two groups. However, the methods used to carry out the randomisation process were not described sufficiently (McMurray 2002; Fogelfeld 2017; Guo 2022; MEMO 2011; Steed 2005).

Two studies were judged to have a low risk of bias and provided sufficient details on how the randomisation process was carried out. These included a random assignment to one of the two groups (1:1 ratio) and stratified block randomisation (Kopf 2012; MESMI 2010).

Allocation concealment

Seven studies were judged to have an unclear risk of bias for allocation concealment. Methods used to ensure the allocation of treatment groups were concealed and were not mentioned in six studies (C‐DIRECT 2019; Fogelfeld 2017; Guo 2022; Kopf 2012; McMurray 2002; MEMO 2011). One study provided insufficient information about allocation concealment (Steed 2005).

One study was judged to have a low risk of bias by providing sufficient details on how the allocation of treatment groups was concealed. Following recruitment, participants were allocated code numbers before enrolment and randomised to the intervention or control group (1:1 ratio) by an off‐site statistician. The people collecting data and assessing outcomes were blinded to group assignment. The identity of all enrolled and randomised participants to receive the intervention was kept in a locked cabinet in the chief researcher’s office (MESMI 2010).

Blinding

Performance bias

The blinding of participants and personnel was assessed separately based on whether the outcomes were subjective or objective. Objective outcomes are unlikely to be influenced by the blinding of participants and personnel compared to subjective outcomes.

For objective outcomes, six studies were judged to have a low risk of bias for blinding participants and personnel (Fogelfeld 2017; Kopf 2012; MEMO 2011; MESMI 2010; Steed 2005; McMurray 2002), and two judged unclear (C‐DIRECT 2019; Guo 2022).

For subjective outcomes, all but one study (McMurray 2002) were judged to be at high risk of bias for blinding of participants and personnel (C‐DIRECT 2019; Fogelfeld 2017; Guo 2022; Kopf 2012; Steed 2005; MEMO 2011; MESMI 2010). McMurray 2002 judged a low risk of bias, as cross‐over of participants and study personnel was maintained throughout the study.

Detection bias

The blinding of outcome assessors was assessed separately based on whether the outcomes were subjective or objective. Compared to subjective outcomes, the blinding of outcome assessors is unlikely to influence some objective outcomes.

For objective outcomes, seven studies were judged to have a low risk of bias detection bias for blinding outcome assessors (C‐DIRECT 2019; Kopf 2012; Fogelfeld 2017; MEMO 2011; MESMI 2010; Steed 2005; McMurray 2002). Guo 2022 was judged to have an unclear risk of detection bias.

For subjective outcomes, five studies were judged to have a high risk of bias for blinding outcome assessors (Fogelfeld 2017; Guo 2022; Kopf 2012; McMurray 2002; Steed 2005). C‐DIRECT 2019, MEMO 2011 and MESMI 2010 were judged to have a low risk of bias.

Incomplete outcome data

Two studies were judged to have a high risk for attrition bias (Kopf 2012; Steed 2005). There was low to moderate loss‐to‐follow‐up at 12 months. Loss to follow‐up was 2% in the intervention group and 11% in the control group. No reasons were provided for loss‐to‐follow‐up (Kopf 2012). Kopf 2012 also had a higher proportion of patients in the intervention group with a history of myocardial infarction compared to the control group at baseline (22.0% versus 4.26%). The attrition rate for Steed 2005 was high (28%); however, they reported the individuals who did and did not complete follow‐up assessments did not differ significantly at baseline. The self‐management programme's efficacy reported that drop‐outs had significantly higher baseline HbA1c than people who completed the education programme.

Fogelfeld 2017 had an unclear risk of bias for incomplete data. Each group had low to moderate attrition rates: the multifactorial education intervention group (23%) and the usual care control group (12%).

Five studies were judged to have a low risk of bias for incomplete data (C‐DIRECT 2019; Guo 2022; McMurray 2002; MEMO 2011; MESMI 2010). McMurray 2002 had no loss to follow‐up. MEMO 2011 and Guo 2022 accounted for all participants from the start to the end of the studies. The attrition rate was low (< 10% in each treatment arm). MESMI 2010 accounted for all participants from the start to the end of the study. Overall, the attrition rates of both arms were low: education (7.7%) and usual care (4.8%). Not all participants had their blood test results included for eGFR and SCr because tests conducted in primary care were not always recorded in the participant’s hospital medical history. According to the Cochrane Handbook for Systematic Reviews of Interventions, we recalculated ITT using 'Case Available Analysis' (dichotomous data) or 'Last Observation Carried Forward' (continuous data) (Higgins 2022).

Selective reporting

Six studies were judged to have an unclear risk of bias for selective reporting (Fogelfeld 2017; Guo 2022; Kopf 2012; McMurray 2002; MESMI 2010; Steed 2005). Kopf 2012 had some results missing for outcomes recorded at baseline (anxiety and eating disorder components of the PHQ). All planned outcomes (as reported in the methods section) were reported in the results for all eight studies. However, no trial registration or a priori‐published protocols were available. McMurray 2002 had some clinically important outcomes missing, such as the incidence of CV disease.

One study was judged to have a low risk of bias. All outcomes planned in the trial registration and a priori‐published protocol were reported methods for MESMI 2010.

C‐DIRECT 2019 had a high risk of bias because some outcomes in the protocol were not reported in the study publication.

Other potential sources of bias

Fogelfeld 2017 was judged to be at high risk of bias. Conflicts of interest or disclosures were not reported, the study received pharmaceutical funding from Sanofi, and the management of this potential conflict was not made explicit.

C‐DIRECT 2019 had a low risk of bias.

The risk of bias for the remaining six studies was judged to be unclear (Guo 2022; Kopf 2012; MEMO 2011; MESMI 2010; McMurray 2002; Steed 2005).

Effects of interventions

See: Table 1

Education programmes plus routine care versus routine care alone

Death

All‐cause death

Education programmes plus routine care compared to routine care alone may make little or no difference to all‐cause death at a mean of nine months follow‐up (Analysis 1.1.1 (4 studies, 424 participants): RR 0.83 95% CI 0.31 to 2.19; I² = 0%; low certainty evidence) (C‐DIRECT 2019; Kopf 2012; MEMO 2011; MESMI 2010).

1.1. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 1: Death

McMurray 2002 (83 participants) reported that the all‐cause death was not different at 12 months, but the specific number of events was not reported. We attempted to contact the authors for details but received no response.

DKD‐related death (total and specific death rates from causes attributable to DKD)

Kopf 2012 (110 participants) reported zero DKD‐related deaths in the intervention and routine care group at 12 months follow‐up (Analysis 1.1.2)

CV disease‐related death

We are uncertain if the education programmes made any difference to CV disease‐related death at a mean of 12 months follow‐up due to very low certainty evidence (Analysis 1.1.3 (2 studies, 289 participants): RR 0.85, 95% CI 0.26 to 2.73; I² = 0%) (Kopf 2012; MEMO 2011).

HbA1c

HbA1c (%)

C‐DIRECT 2019, Kopf 2012, MEMO 2011, MESMI 2010 and Steed 2005 reported HbA1c (%).

Education programmes, compared to routine care alone, probably decrease HbA1c (%) at a mean of 13.5 months follow‐up (Analysis 1.2 (4 studies, 467 participants): MD ‐0.42%, 95% CI ‐0.53 to ‐0.31; I² = 0%; moderate certainty evidence) (Kopf 2012; MEMO 2011; Steed 2005; C‐DIRECT 2019).

1.2. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 2: HbA1c [%]

MESMI 2010 (80 participants) reported the median and interquartile range for HbA1c (%). In the education programme plus routine care group, the median HbA1c was 7% at three months, 7.5% at six months, and 7% at nine months follow‐up. For the routine care group, it was 7% at three months, 7% at six months, and 8% at nine months.

McMurray 2002 (83 participants) reported that HbA1c levels declined from 6.9% to 6.2% in the education programmes group, whereas the routine care group results were unchanged at 7% (P < 0.005). They also reported that the reduction in blood glucose and HbA1c levels wasn't associated with increased hypoglycaemia. We attempted to contact the authors for the mean and standard deviation but received no reply.

Attaining a HbA1c ≤ 6.5% (48 mmol/mol)

MEMO 2011 reported that attaining an HbA1c ≤ 6.5% (48 mmol/mol) at 18 months may be decreased with routine care, compared to the education programmes (Analysis 1.3 (179 participants): RR 2.43, 95% CI 1.37 to 4.32; low certainty evidence).

1.3. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 3: Attaining HbA1c < 6.5%

Kidney failure

Kopf 2012 reported the incidence of kidney failure, but the effect is unclear due to few reported events (Analysis 1.4 (110 participants): RR 3.22, 95% CI 0.13 to 77.41) (very low certainty evidence).

1.4. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 4: Kidney failure

Patient‐orientated measures of knowledge, self‐management, and behavioural changes

Attitude scales

Steed 2005 (97 participants) reported a MD in participants' attitude scales for seriousness, treatment effectiveness and personal control in participants who had an education programme plus routine care group compared to routine care at five weeks (end of treatment) and three months follow‐up.

Education programmes compared to routine care may make little or no difference in the attitude toward the seriousness of disease at the end of treatment (Analysis 1.5.1: MD 0.09, 95% CI ‐0.24 to 0.42) and at the end of follow‐up (Analysis 1.6.1: MD 0.11, 95% CI ‐0.24 to 0.46) (low certainty evidence). However, a difference was reported between the groups for the attitude scale for treatment effectiveness at the end of treatment (Analysis 1.5.2: MD 0.25, 95% CI 0.07 to 0.43) and at the end of follow‐up (Analysis 1.6.2: MD 0.24, 95% CI ‐0.00 to 0.48) (low certainty evidence).

1.5. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 5: Patient‐oriented measures: beliefs at the end of treatment (attitude scales)

1.6. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 6: Patient‐oriented measures: beliefs at the end of follow‐up (attitude scales)

Education programmes, compared to routine care, may make little or no difference in attitude (personal control) at the end of treatment (Analysis 1.5.3: MD 0.31, 95% CI ‐0.03 to 0.65). However, personal control at three months follow‐up may be slightly increased with the education programmes compared to routine care (Analysis 1.6.3: MD 0.31 95% CI 0.01 to 0.61) (low certainty evidence).

Knowledge of diabetes

McMurray 2002 (83 participants) reported that after 12 months of follow‐up, education programmes compared to routine care may increase all 11 items related to specific diabetes knowledge in people receiving dialysis (Analysis 1.7) (all low certainty evidence).

1.7. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 7: Patient‐oriented measures: knowledge of diabetes at the end of treatment

• Diagnosis (MD 0.80, 95% CI 0.54 to 1.06)

• Monitoring (MD 1.30, 95% CI 0.92 to 1.68)

• Hypoglycaemia (MD 1.10, 95% CI 0.81 to 1.39)

• Hyperglycaemia (MD 0.50, 95% CI 0.22 to 0.78)

• Medication (insulin) (MD 1.40, 95% CI 0.90 to 1.90)

• Oral medication (MD 0.70, 95% CI 0.38 to 1.02)

• Personal health habits (MD 1.40, 95% CI 1.06 to 1.74)

• Diet (MD 0.40, 95% CI 0.07 to 0.73)

• Exercise (MD 0.80, 95% CI 0.49 to 1.11)

• Chronic complications (MD 0.90, 95% CI 0.59 to 1.21)

• Living with diabetes and coping with stress (MD 0.60, 95% CI 0.21 to 0.99).

Steed 2005 (97 participants) reported that education programmes plus routine care may improve general knowledge of diabetes at the end of the five‐week intervention (Analysis 1.8.1: MD 15.82, 95% CI 8.39 to 23.25) and after three months of follow‐up (Analysis 1.8.2: MD 14.39, 95% CI 7.45 to 21.33) (low certainty evidence) compared to routine care alone.

1.8. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 8: Patient‐oriented measures: general knowledge of diabetes

Measures of patient empowerment and self‐efficacy

Steed 2005 (97 participants) reported education programmes plus routine care may improve patient total self‐efficacy at the end of the five‐week intervention (Analysis 1.9.1: MD 19.00, 95% CI 12.58 to 25.42), but no difference was reported at the end of the three‐month follow‐up (Analysis 1.10.1: MD 2.97, 95% CI ‐3.43 to 9.37) (low certainty evidence).

1.9. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 9: Patient‐oriented measures: self‐efficacy at the end of treatment

1.10. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 10: Patient‐oriented measures: self‐efficacy at the end of follow‐up

Steed 2005 (97 participants) reported education programmes may make little or no difference to self‐efficacy related to HBGM compared to routine care at the end of the five‐week intervention (Analysis 1.9.2: MD 6.96, 95% CI ‐2.87 to 16.79). However, education programmes may increase self‐efficacy related to HBGM after three months of follow‐up Analysis 1.10.2: MD 11.28, 95% CI 1.92 to 20.64) (low certainty evidence).

Steed 2005 (97 participants) reported education programmes may make little or no difference to diet after five weeks of education programmes (Analysis 1.9.3: MD 0.74, 95% CI ‐7.51 to 8.99) or after three months of follow‐up compared to routine care (Analysis 1.10.3: MD 3.46, 95% CI ‐4.32 to 11.24) (low certainty evidence).

Steed 2005 (97 participants) reported education programmes may make little or no difference to exercise after five weeks of education programmes (Analysis 1.9.4: MD 3.64, 95% CI ‐7.04 to 14.32) or after three months of follow‐up compared to routine care (Analysis 1.10.4: ME 8.28, 95% CI ‐2.04 to 18.60) (low certainty evidence).

C‐DIRECT 2019 (42 participants) reported there may be little or no difference between education programmes and routine care with the diabetes self‐efficacy scale after three months of follow‐up (Analysis 1.10.5: MD ‐0.57 95% CI ‐1.65 to 0.51) (low certainty evidence).

Patient behavioural changes

McMurray 2002 (83 participants) reported that education programmes compared to routine care may improve self‐management of checking feet (Analysis 1.11.1: RR 1.63, 95% CI 1.01 to 2.63), using lotion (Analysis 1.11.2: RR 9.71, 95% CI 2.45 to 38.56) and wearing appropriate shoes and socks (Analysis 1.11.3: RR 4.39, 95% CI 1.87 to 10.32), after 12 months of treatment. However, there may be little or no difference in HDGM (Analysis 1.11.4: RR 1.20, 95% CI 0.81 to 1.79), carrying carbohydrate (Analysis 1.11.5: RR 1.90, 95% CI 0.93 to 3.87) or eye examination (Analysis 1.11.6: RR 1.48, 95% CI 0.95 to 2.29).

1.11. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 11: Patient‐oriented measures: self‐management behaviour changes at the end of treatment

Steed 2005 (100 participants) reported there may be beneficial effects of educational programmes on behaviour change at the end of treatment for general diet (Analysis 1.12.1: MD 0.73, 95% CI 0.10 to 1.36), specific diet (Analysis 1.12.2: MD 1.02, 95% CI 0.42 to 1.62), and HBGM (Analysis 1.12.4: MD 2.13, 95% CI 1.18 to 3.08), but not for exercise (Analysis 1.12.3: MD 0.76, 95% CI ‐0.11 to 1.63), foot care (Analysis 1.12.5: MD 0.19, 95% CI ‐0.72 to 1.10) or quitting smoking (Analysis 1.11.7: RR 0.81, 95% CI 0.09 to 7.58).

1.12. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 12: Patient‐oriented measures: behavioural changes at the end of treatment

The benefits were no longer seen at the end of follow‐up for general diet (Analysis 1.13.1 (2 studies, 142 participants): MD 0.09, 95% CI ‐0.46 to 0.64; I² = 0%), specific diet (Analysis 1.13.2 (2 studies, 142 participants): MD 0.46 95% CI ‐0.02 to 0.93; I² = 0%) or HBGM (Analysis 1.13.4 (2 studies, 142 participants): MD 0.62 95% CI ‐1.23 to 2.48; I² = 76%). There may be little or no difference between the groups at the end of follow‐up for either exercise (Analysis 1.13.3 (2 studies, 142 participants): MD 0.45 95% CI ‐0.28 to 1.18; I² = 0%) or foot care (Analysis 1.13.5 (2 studies, 142 participants): MD 0.06 95% CI ‐0.70 to 0.83; I² = 0%) (all low certainty evidence).

1.13. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 13: Patient‐oriented measures: behavioural changes at the end of follow‐up

Kidney function measures

Estimated glomerular filtration rate

MEMO 2011 (179 participants) reported there may be little or no difference in eGFR between the groups at 18 months follow‐up (Analysis 1.14: MD 0.46 mL/min/1.73 m², 95% CI ‐3.71 to 4.63; low certainty evidence).

1.14. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 14: Estimated GFR [mL/min/1.73 m²]

Kopf 2012 reported a median eGFR of 85.9 mL/min/1.73 m² (interquartile range (IQR) 83.0 to 88.7; 52 participants) in the education programme group at one‐year follow‐up. The reported median for the routine care group was 87 mL/min/1.73 m² (IQR 83.7 to 90.3; 48 participants) (P = 0.08). At the two‐year follow‐up, a median eGFR of 82.7 mL/min/1.73 m² (IQR 79.0 to 86.5; 51 participants) was reported in the education programme group, and 84.4 mL/min/1.73 m² (IQR 80.0 to 88.7; 43 participants) in the routine care group (P = 0.09).

MESMI 2010 reported at three months follow‐up, the median eGFR was 53 mL/min/1.73 m² (IQR 35 to 64; 39 participants) in the education programme group and 40 mL/min/1.73 m² (IQR 27 to 56; 41 participants) in the routine care group. At nine months follow‐up, the median eGFR was 48 mL/min/1.73 m² (IQR 38 to 76; 39 participants) in the education programme group and 46 mL/min/1.73 m² (IQR 32 to 72; 41 participants) in the routine care group.

Serum creatinine

Kopf 2012 reported a median SCr of 0.086 mmol/L (IQR 0.080 to 0.092; 47 participants) in the education programme group and 0.084 mmol/L (IQR 0.076 to 0.091; 42 participants) in the routine care group, at three years follow‐up (P = 0.10).

MESMI 2010 reported a median SCr of 0.117 mmol/L (IQR 0.082 to 0.144; 39 participants) in the education programme group and 0.108 mmol/L (IQR 0.089 to 0.171; 41 participants) in the routine care group at three years follow‐up.

Urinary albuminuria‐creatinine ratio

MEMO 2011 (189 participants) reported there may be little or no difference in UACR between the education programme group and routine care at 18 months of follow‐up (Analysis 1.15: MD 0.35 mg/g, 95% CI ‐1.01 to 1.71; low certainty evidence).

1.15. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 15: Urinary albumin‐creatinine ratio [mg/g]

Kopf 2012 reported a median UACR of 32.2 mg/g (IQR 9.8 to 76.3; 47 participants) in the education programme group and 31.6 mg/g (IQR 12.1 to 83.0; 42 participants) in the routine care group, at three years follow‐up (P = 0.05).

Blood pressure

Systolic blood pressure

MEMO 2011 (179 participants) reported that SBP may be lower in the education programme group compared to the routine care group at 18 months follow‐up (Analysis 1.16.1: MD ‐11.12 mm Hg, 95% CI ‐16.38 to ‐5.86; low certainty evidence).

1.16. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 16: Blood pressure [mm Hg]

Diastolic blood pressure

MEMO 2011 (179 participants) reported that DBP may be lower in the education programme group compared to the routine care group at 18 months follow‐up (Analysis 1.16.2: MD ‐5.43 mm Hg, 95% CI ‐9.12 to ‐1.74; low certainty evidence).

Glycaemic events

Hypoglycaemia

MEMO 2011 (179 participants) reported education programmes compared to routine care alone may make little or no difference to hypoglycaemia at 18 months follow‐up (Analysis 1.17.1: RR 0.85, 95% CI 0.67 to 1.08; low certainty evidence).

1.17. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 17: Glycaemic events

Serious hypoglycaemia

MEMO 2011 (179 participants) reported education programmes compared to routine care alone may make little or no difference to serious hypoglycaemia at 18 months follow‐up (Analysis 1.17.2: RR 0.08, 95% CI 0.00 to 1.33; low certainty evidence).

McMurray 2002 reported no severe hypoglycaemic episodes in the education programme group, and it is unclear if this extends to the control group. We contacted the authors for the specific numbers, as these were not reported, but received no response.

Non‐fatal cardiovascular events

Kopf 2012 (110 participants) reported education programmes, compared to routine care alone, may make little or no difference to total cardiovascular events (Analysis 1.18.1: RR 1.25, 95% CI 0.45 to 3.49).

1.18. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 18: Non‐fatal cardiovascular events

Education programmes compared to routine care alone may make little or no difference to stroke (Analysis 1.18.2 (2 studies, 289 participants): RR 4.06, 95% CI 0.45 to 36.26; I² = 0%) or MI (Analysis 1.18.3 (2 studies, 289 participants): RR 1.18 95% CI 0.41, 3.43; I² = 0%).

MEMO 2011 (179 participants) reported education programmes, compared to routine care alone, may make little or no difference to heart failure (Analysis 1.18.4: RR 1.98, 95% CI 0.18 to 21.42).

Quality of life

The PHQ was used to assess levels of stress, depression and other psychiatric co‐morbidities, with a lower score indicating less stress. Kopf 2012 (103 participants) reported a lower score with the education programme compared to routine care (Analysis 1.19.1: MD ‐1.70, 95% CI ‐3.09 to ‐0.31; 1 study, 103 participants) at 12 months follow‐up.

1.19. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 19: Quality of life

C‐DIRECT 2019 (42 participants) reported CKD‐related QoL at three months follow‐up using the KDQoL questionnaire, with higher scores indicating better QoL. C‐DIRECT 2019 reported there may be no differences between the education programme group and the routine care group for the physical composite summary (Analysis 1.19.2: MD 2.13, 95% CI ‐5.14 to 9.40), the mental composite summary (Analysis 1.19.3: MD ‐8.43, 95% CI ‐22.69 to 5.83), the kidney disease composite summary (Analysis 1.19.4: MD ‐4.55, 95% CI ‐12.19 to 3.09), and the general health composite summary (Analysis 1.19.5: MD ‐0.63, 95 % CI‐5.31 to 4.05) (all low certainty evidence).

A questionnaire to evaluate the patient's QoL based on diabetes condition and complications was adapted from the standardised Diabetes Form 2.1 (Hoogwerf 1992). McMurray 2002 reported strong evidence for the improvement in the QoL assessment domains of diabetic symptoms (P < 0.001) and health perception (P < 0.002) in the education programme plus routine care group, compared to routine care. There was no improvement in the categories of social functioning, role limitations and mental health score reported.

Steed 2005 reported that diabetes‐specific QoL, using the Audit of Diabetes Dependent Quality of Life measure (ADDQoL) (Bradley 1999), and generic QoL using the UK SF‐36 (Jenkinson 1996). Patients who received the education programme only demonstrated improved diabetes‐specific QoL during follow‐up (for three months after the end of treatment) (ANCOVA = 9.33; P < 0.01) compared to the routine care group. UK SF‐36 data on general QoL was not reported.

We contacted the authors of McMurray 2002 and Steed 2005 for the data to include in our meta‐analysis but were unsuccessful.

See Appendix 3 for the assessment tools used.

Lipids

Total cholesterol

MEMO 2011 (179 participants) reported total cholesterol may be lower in the education programme group at 18 months follow‐up (Analysis 1.20.1: MD ‐0.35 mmol/L, 95% CI ‐0.63 to ‐0.07; low certainty evidence), compared to the routine care group.

1.20. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 20: Lipids [mmol/L]

HDL cholesterol

MEMO 2011 (179 participants) reported education programmes, compared to routine care, may make little or no difference to HLD cholesterol at 18 months follow‐up (Analysis 1.20.2: MD ‐0.03 mmol/L, 95% CI ‐0.09 to 0.03; low certainty evidence).

LDL cholesterol

MEMO 2011 (179 participants) reported LDL cholesterol may be lower in the education programme group at 18 months follow‐up (Analysis 1.20.3: MD ‐0.40 mmol/L, 95% CI ‐0.65 to ‐0.14; 179 participants; low certainty evidence) compared to the routine care group.

Triglycerides

MEMO 2011 (179 participants) reported education programmes, compared to routine care, may make little or no difference to triglycerides at 18 months follow‐up (Analysis 1.20.4: MD 0.07 mmol/L, 95% CI ‐0.38 to 0.52; low certainty evidence).

Adverse events

Non‐fatal adverse events

MEMO 2011 (179 participants) reported education programmes, compared to routine care, may make little or no difference to non‐fatal adverse events at 13.5 months follow‐up (Analysis 1.21: RR 1.03, 95% CI 0.89 to 1.18; low certainty evidence).

1.21. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 21: Adverse events: non‐fatal (including hypoglycaemic and CVD events)

Serious adverse events (including deaths)

There may be little or no difference in serious adverse events between treatment groups at 18 months follow‐up (Analysis 1.22 (2 studies, 289 participants): RR 0.76, 95% CI 0.36 to 1.62; I² = 58%; low certainty evidence).

1.22. Analysis.

Comparison 1: Educational programmes plus routine care versus routine care alone, Outcome 22: Serious adverse events: emergency hospitalisation or death (including serious hypoglycaemic and CVD events)

McMurray 2002 reported no limb amputations in the education programme group, whereas the routine care group had five lower‐extremity amputations and two‐finger amputations during the 12‐month study. Overall, the education group had a significantly lower hospitalisation rate for diabetes, peripheral vascular disease, infection, and amputation‐related admissions (P < 0.05). The data could not be included in the meta‐analysis as not all the number of events were reported.

Multidisciplinary, multifactorial education programmes versus routine care

Death

None of the included studies reported all‐cause death, DKD‐related death, or CV disease‐related death.

HbA1c

Fogelfeld 2017 (120 participants) reported there may be little or no difference between the groups for HbA1c at 12 months follow‐up (Analysis 2.1: MD ‐0.40%, 95% CI ‐1.00 to 0.20; low certainty evidence). However, patients who received the education programme were more likely to attain a HbA1C% < 7% (53.0 mmol/mol) (50.0% versus 31.6%, P = 0.05) at follow‐up (low certainty evidence).

2.1. Analysis.

Comparison 2: Multidisciplinary, multifactorial education programmes versus routine care, Outcome 1: HbA1c [%]

Kidney failure

Fogelfeld 2017 (120 participants) reported there may be little or no difference between the groups for kidney failure at the end of the intervention (two years) (Analysis 2.2: RR 0.47, 95% CI 0.22 to 1.01; low certainty evidence).

2.2. Analysis.

Comparison 2: Multidisciplinary, multifactorial education programmes versus routine care, Outcome 2: Kidney failure

Patient‐oriented measures

None of the included studies reported behaviour change, knowledge or self‐efficacy.

Kidney function measures

eGFR

Fogelfeld 2017 (120 participants) reported there may be little or no difference between the groups for eGFR at the end of the intervention (two years) (Analysis 2.3: MD 2.03 mL/min/1.73 m², 95% CI ‐3.44 to 7.50; low certainty evidence).

2.3. Analysis.

Comparison 2: Multidisciplinary, multifactorial education programmes versus routine care, Outcome 3: Estimated GFR [mL/min/1.73 m²]

Albuminuria

Fogelfeld 2017 reported a median UACR of 783.4 (IQR 215 to 2209) in the education group and 748.0 (IQR 218 to 2260) in the control group at two years follow‐up.

Blood pressure

Systolic blood pressure

Fogelfeld 2017 (120 participants) reported there may be little or no difference between the groups for SBP at the end of the intervention (two years) (Analysis 2.4.1: MD ‐0.19 mm Hg, 95% CI ‐6.41 to 6.03; very low certainty evidence).

2.4. Analysis.

Comparison 2: Multidisciplinary, multifactorial education programmes versus routine care, Outcome 4: Blood pressure [mm Hg]

Diastolic blood pressure

Fogelfeld 2017 (120 participants) reported there may be little or no difference between the groups for DBP at the end of the intervention (two years) (Analysis 2.4.2: MD ‐3.40 mm Hg, 95% CI ‐8.02 to 1.22; very low certainty evidence).

Glycaemic events

Hypoglycaemia

There may be little or no difference between treatment groups for hypoglycaemia at 12 months follow‐up (Analysis 2.5.1 (2 studies, 210 participants): RR 0.57, 95% CI 0.10, 3.36; I² = 83%; low certainty evidence). The percentage of hypoglycaemia was either self‐measured blood glucose < 70 mg/dL or reported symptomatic hypoglycaemia in all six‐month visits.

2.5. Analysis.

Comparison 2: Multidisciplinary, multifactorial education programmes versus routine care, Outcome 5: Glycaemic events

Hyperglycaemia

Guo 2022 (90 participants) reported there may be little or no difference between the groups for hyperglycaemia (follow‐up unknown) (Analysis 2.5.2: RR 0.14, 95% CI 0.02 to 1.11; low certainty evidence).

Non‐fatal cardiovascular events

None of the included studies reported total CV disease events (stroke, MI, heart failure, or peripheral vascular disease).

Quality of life

None of the included studies reported QoL.

Lipids

HDL cholesterol

Fogelfeld 2017 (120 participants) reported there may be little or no difference between the groups for HDL cholesterol at the end of the intervention (two years) (Analysis 2.6.1: MD 0.03 mg/dL, 95% CI ‐4.39 to 4.45; very low certainty evidence).

2.6. Analysis.

Comparison 2: Multidisciplinary, multifactorial education programmes versus routine care, Outcome 6: Lipids [mg/dL]

LDL cholesterol

Fogelfeld 2017 (120 participants) reported there may be little or no difference between the groups for LDL cholesterol at the end of the intervention (two years) (Analysis 2.6.2: MD ‐5.87 mg/dL, 95% CI ‐20.11 to 8.37).

Triglycerides

Fogelfeld 2017 reported lower median triglycerides (125.0 mg/dL; IQR 80 to 187) in the education programme group compared to the routine care group (141.0 mg/dL; IQR 109 to 184) at the end of the intervention (two years).

Adverse events

None of the included studies reported adverse events.

Subgroup analysis

Pre‐specified subgroup analyses were not possible due to the limited number of studies included for each outcome.

Sensitive analysis

It was not possible to perform sensitivity analyses due to the limited number of included studies for each outcome.

Publication bias

It was not possible to check for publication bias due to the limited number of included studies for each outcome examined.

Discussion

Summary of main results

The eight studies, including 840 people with CKD (from early‐stage pre‐dialysis to dialysis) and DM, found that education programmes may improve knowledge about diagnosis, monitoring and regulating diabetes control, managing medications and personal health habits. These included diet and exercise, hypoglycaemia and hyperglycaemia, living with diabetes and coping with stress. Improvements in self‐efficacy after treatment were also evident in people who received an education programme compared to those who received routine care alone. The increased knowledge and self‐efficacy may have contributed to improved self‐management behaviours after treatment, such as checking feet, using lotion and wearing appropriate shoes and socks, monitoring blood glucose and improving diet, as well as lower HbA1c, LDL cholesterol and SBP and DBP. However, the limited effect on behaviour change at the end of the follow‐up suggests that ongoing education might be needed after treatment to ensure important self‐management behaviour continues. These important patient preference outcomes show potential benefits with little harm (SONG‐CKD 2018; Tong 2012).

Despite evidence of improved knowledge, self‐efficacy, and behaviour change, the studies included in this review had uncertainty around hard clinical endpoints such as death, kidney failure, and cardiovascular outcomes due to lack of events, likely because of the studies' short duration. Given the advanced stage of CKD and DM in many of the participants, it is unclear if there would be significant changes in these clinical endpoints even if the studies were of longer duration. Longer‐term studies that focus on validated surrogate outcomes, such as eGFR slope related to long‐term adverse kidney events, are necessary. These outcomes are particularly important for people with early‐stage CKD and DM.

Overall completeness and applicability of evidence

This review was based on a highly sensitive search. One major limitation is the small number of included studies, which may impact the generalisability of the findings for clinical practice.

Characteristics of participants

In this review, the included studies were not representative of all cultures, as studies were largely conducted in the USA, Japan, Germany, Australia, and the UK. It has been reported that cultural factors also play a role in the effectiveness of educational interventions (Hawthorne 2008). Ethnic minority groups in upper‐middle and high‐income countries tend to be socio‐economically disadvantaged and have a higher prevalence of T2DM than the majority population (Smedley 2002). They also have a higher burden of diabetes and CKD (Cowie 1989; Pugh 1988). A Cochrane review (Hawthorne 2008) showed that culturally appropriate diabetes health education appears to have short‐term effects on glycaemic control and knowledge of diabetes and healthy lifestyles. Whether education programmes have similar effects regarding content and delivery is still uncertain for people with different cultural backgrounds. It should also be noted that in C‐DIRECT 2019, both ITT and per‐protocol analysis showed ethnicity had a significant effect on several outcomes, indicating lower QoL, self‐management skills and higher depression for Chinese relative to non‐Chinese, irrespective of study arm.

Measurement of outcomes

It is well known that for those with both DM and CKD, the outlook is far worse than for either condition alone because this combination is a powerful predictor of major adverse cardiovascular events and death (KDOQI 2007; KDIGO 2022). The most important treatment goal for co‐existing DM and CKD is to reduce or delay the onset of cardiovascular events and kidney failure, ultimately prolonging survival and improving QoL (KDIGO 2022). However, the eight included studies focused mainly on surrogate endpoints (e.g. patients' knowledge of diabetes and self‐management behavioural changes). A limitation of this review is the short‐term follow‐up of the included studies and, in turn, the lack of sufficient follow‐up for important clinical outcomes, such as cardiovascular events. Strategies to promote glycaemic control and minimise CKD progression depend on the ability and willingness of the patients to change and subsequently maintain appropriate behaviours. A strength of this review was the reporting of patient‐important outcomes such as self‐efficacy and self‐management. Two meta‐analyses have demonstrated that enhancing adherence to a diabetes regimen resulted in better glycaemic control, particularly if the interventions were repetitive and ongoing (Ellis 2004; Norris 2001).

Adverse effects are as important as the efficacy of the interventions in clinical studies. Due to the lack of data, we were unable to report adverse events specifically resulting from educational programmes. It might be that the education programmes had little to no adverse effects. However, no conclusions can be made due to the limited reporting.

Quality of the evidence

In general, most studies exhibited study limitations, or there was limited reporting of methodological details. Not all studies had a published protocol or were registered in a clinical trial registry. The overall risk of bias was low for objective outcomes and attrition bias, unclear for selection bias, reporting bias and other biases, and high for subjective outcomes. The lack of blinding for subjective measures may impact the certainty of the evidence more so than objective outcomes. To control for this, we assessed blinding for subjective and objective outcomes separately.

Methodologically, less rigorous studies show larger differences between treatment and control groups than those conducted with better rigour (Kjaergard 1999; Moher 1998; Moher 2009; Schulz 1995). Schulz 1995 found that odd ratios were exaggerated by up to 30% for studies that did not have clear concealment and 41% for inadequately concealed studies. Many of the outcomes had limited data from only one study and included few participants, increasing imprecision.

It was also not possible to perform a funnel plot to assess the degree of publication bias because of the limited number of studies for each outcome. Although we have undertaken extensive searches for published material, we still can not exclude the possibility that studies with negative findings remain unpublished. To avoid potential publication bias, we also included relevant conference abstract publications and data from trial registries that may not have gone on to full publication.

Potential biases in the review process

This systematic review's strengths include the clear definition of the objectives and scope of research and the requirement that two authors reach a consensus on all data elements. Another major strength of this review is the collaboration of multidisciplinary researchers who participated in its development. This review was undertaken by investigators who are skilled at employing highly systematic and unbiased methods to collect, review and synthesise data from published literature. Throughout the course of this review, there was frequent input from the co‐investigators, who are clinical and methodological content experts. The review authors are independent and have no affiliation with any trial investigators or conflict of interests, and the review received no industry funding. The small number of studies may limit the power of statistical testing to detect important differences.

Agreements and disagreements with other studies or reviews

A recent cross‐sectional study in patients with early‐stage CKD reported that improving self‐efficacy is an important mediator between knowledge and self‐management (Chuang 2021). It is plausible that the improvement in self‐efficacy and knowledge observed in the education intervention group in our review may have led to meaningful self‐management behaviour change and contributed to the improved glycaemic control for people with DM and CKD. A systematic review of DM self‐management education interventions for people with T2DM in the Asian Western Pacific region also found that in eight out of the 21 included studies, there was an improvement in glycaemic control in DM participants, and they reported improvement in HbA1c levels (Mohamed 2019).

Duke 2009 compared individual education programmes to group education sessions or usual care (9 studies; 1359 participants) in people with DM. Similarly to our findings, the review found no long‐term studies, and the overall certainty of the evidence was low. Compared to usual care, individual face‐to‐face education had little or no effect over a 12 to 18‐month period. However, there was a benefit in people with a higher mean baseline HbA1c > 8%. However, the effect on self‐management and self‐efficacy was unclear due to a lack of available data.

While Duke 2009 showed no difference between individual education and group education, another systematic review of patients with CKD that included observational studies highlighted the effectiveness of multifaceted education interventions and that characteristics of effective interventions included teaching sessions that involved not only groups of patients but also their families (Lopez‐Vargas 2016). A limitation of our review is that we were unable to undertake a subgroup analysis comparing group‐based and individual‐based education programmes. However, we made another separate comparison between education programmes plus multidisciplinary, co‐ordinated care versus usual care. We did not find any differences in any outcomes for this comparison pair, largely due to having one study included and low certainty of the evidence. A multidisciplinary team was listed by Lopez‐Vargas 2016 as an important characteristic of an effective education programme. A meta‐analysis (3 studies; 327 participants) found that multidisciplinary management of CKD and DM was associated with an improvement of HbA1c, compared with standard usual care at a mean 13‐month follow‐up (Helou 2016).

Authors' conclusions

Implications for practice.

Education programmes may have positive effects on the improvement of patients' knowledge of DM, resulting in self‐management behavioural changes for people with T1DM or T2DM on dialysis or people with T2DM with moderately increased albuminuria (A2). However, people with both CKD and DM, and clinicians should be aware that the effects on clinical endpoints are uncertain due to the limited availability of high‐quality data. Recent guidelines for the management of CKD and DM suggest structured education is critical to engaging people with CKD and DM to self‐manage their disease and participate in the necessary shared decision‐making regarding their management plan (KDIGO 2022). While the data on the benefits and harms in our review are uncertain, it supports these recommendations due to the potential benefits and little expected harms of an education programme.

Implications for research.

The promising results from these eight studies warrant further research. To confirm the available evidence, larger numbers of participants and high‐quality RCTs are needed. Future studies should address the following features.

Methodology

Reports of RCTs should conform to the recommendations of the CONSORT statement. The 25‐item CONSORT checklist provides information on how the trial was designed, analysed and interpreted. Using this tool encourages standardised reporting of interventions, and a thorough description of the interventions would allow a better comparison of the included studies and be easier to reproduce. Using this tool would aid in assessing the methodological quality of the included studies, and future studies should have detailed reporting of the methods of randomisation and allocation concealment, with clear descriptions of blinding. Particularly for outcome assessors and data assessors, who could be blinded for educational programme research.

Finally, there should be more adequately powered studies. All the eligible studies had small sample sizes. While one of the benefits of meta‐analysis is that a synthesis of inadequately powered studies can yield interesting findings, such meta‐analyses require large numbers of small studies in order to obtain conclusive findings.

Participants

Increasing the diversity of participants in the included studies is required. Recruitment of people with CKD and DM from different subgroups (e.g. ethnicity, culture, socioeconomic status, stage of CKD) is needed to improve the generalisability of the findings on the efficacy and safety of educational programmes. In addition, specific cultural adaptations are needed to address the requirements of local individuals to support self‐management (Mohamed 2019).

Outcomes

CKD outcomes should be based on the SONG‐CKD outcome set, in addition to important clinical outcomes (SONG‐CKD 2018). Including patient‐reported outcomes ensures research reports outcomes that are meaningful and relevant to people with kidney disease, their family, and their clinicians (Gutman 2019; Tong 2012). In addition, future studies should include:

1. Reporting clinically important outcome measures over a long period of time, such as CV events, kidney failure or validated surrogate outcomes (e.g. doubling SCr or ≥ 57% GFR loss), are important endpoints for clinical decision‐making.

2. Reporting important educational outcomes such as changes in knowledge, understanding, attitude, self‐care, and lifestyle behaviours, adherence to treatment regimens, self‐determination and participation in care decision‐making, and psychological adjustment.

3. Adverse events should be critically assessed by standardised monitoring or an effective self‐report system, considering observational data on adverse events while recognising the limitations of RCT data.

4. Standardised reporting of outcomes and more exact data on QoL outcomes, using means rather than median and interquartile ranges. This would allow for meta‐analysis and better comparison of results across studies.

5. Increasing the duration of studies and also the follow‐up time to determine whether the effects are long‐lasting following the intervention.

What's new

Date	Event	Description
22 August 2024	New citation required and conclusions have changed	New comparisons and outcomes added
22 August 2024	New search has been performed	New studies included

History

Protocol first published: Issue 4, 2008
Review first published: Issue 6, 2011

Date	Event	Description
7 May 2014	Amended	Minor copy edit made

Appendices

Appendix 1. Electronic search strategies

Database	Search terms
CENTRAL	MeSH descriptor Patient Education as Topic, this term only MeSH descriptor Health Education, this term only MeSH descriptor Self Care explode all trees MeSH descriptor Adaptation, Psychological explode all trees MeSH descriptor Programmed Instruction as Topic, this term only MeSH descriptor Teaching Materials explode all trees MeSH descriptor Teaching explode all trees MeSH descriptor Learning, this term only MeSH descriptor Behavior Control, this term only MeSH descriptor Behavior Therapy, this term only MeSH descriptor Health Behavior, this term only MeSH descriptor Quality of Life, this term only (health educat* or patient* education or education* program* or health* program*) (patient* and (behav* or educat* or instruct*)) (1 OR 2 OR 3 OR 4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14) MeSH descriptor Diabetes Mellitus, this term only MeSH descriptor Diabetes Mellitus, Type 1, this term only MeSH descriptor Diabetes Mellitus, Type 2 explode all trees (16 OR 17 OR 18) (kidney* or renal* or nephro* or nephritis or glomerulo* or albuminuria*) (19 AND 20) MeSH descriptor Diabetic Nephropathies, this term only (diabetic nephropath* ) "diabetic kidney disease" (22 OR 24) (21 AND 25) (15 AND 26)
MEDLINE	Patient Education as Topic/ Health Education/ exp Self Care/ exp Adaptation, Psychological/ Programmed Instruction as Topic/ exp Teaching Materials/ exp Teaching/ exp Learning/ Behavior control/ Behavior Therapy/ Health Behavior/ "Quality of Life"/ (health educat$ or patient$ education or education$ program$ or health$ program$).tw. (patient$ and (behav$ or educat$ or instruct$)).tw. or/1‐14 Diabetes Mellitus/ exp Diabetes Mellitus,Type 1/ exp Diabetes Mellitus,Type 2/ or/16‐18 (kidney$ or renal$ or nephro$ or nephritis or glomerulo$ or albuminuria$).tw. and/19‐20 Diabetic Nephropathies/ diabetic nephropath$.tw. "diabetic kidney disease".tw or/22‐24 or/21,25 and/15,26
EMBASE	1. patient education/ 2. exp health education/ 3. adjustment/ 4. health program/ 5. teaching/ 6. LEARNING/ 7. behavior control/ 8. Behavior Therapy/ 9. exp Education/ 10. or/1‐9 11. Diabetic Nephropathy/ 12. diabetic kidney disease.tw or daibetic nephropath$.tw 13. or/11‐12 14. and/10,13

Appendix 2. Risk of bias assessment tool

Potential source of bias	Assessment criteria
Random sequence generation Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence	Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimisation (minimisation may be implemented without a random element, and this is considered to be equivalent to being random).
	High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.
	Unclear: Insufficient information about the sequence generation process to permit judgement.
Allocation concealment Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment	Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web‐based, and pharmacy‐controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes).
	High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non‐opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.
	Unclear: Randomisation stated but no information on method used is available.
Blinding of participants and personnel Performance bias due to knowledge of the allocated interventions by participants and personnel during the study	Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
	High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.
	Unclear: Insufficient information to permit judgement
Blinding of outcome assessment Detection bias due to knowledge of the allocated interventions by outcome assessors.	Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.
	High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.
	Unclear: Insufficient information to permit judgement
Incomplete outcome data Attrition bias due to amount, nature or handling of incomplete outcome data.	Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardised difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods.
	High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as‐treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.
	Unclear: Insufficient information to permit judgement
Selective reporting Reporting bias due to selective outcome reporting	Low risk of bias: The study protocol is available and all of the study’s pre‐specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre‐specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre‐specified (convincing text of this nature may be uncommon).
	High risk of bias: Not all of the study’s pre‐specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. sub‐scales) that were not pre‐specified; one or more reported primary outcomes were not pre‐specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta‐analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study.
	Unclear: Insufficient information to permit judgement
Other bias Bias due to problems not covered elsewhere in the table	Low risk of bias: The study appears to be free of other sources of bias.
	High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data‐dependent process (including a formal‐stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem.
	Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias.

Appendix 3. Assessment tools

Assessment tool	Items, scale and direction of effect
PAID: Problem Areas in Diabetes Scale C‐DIRECT 2019	20 items (0 to 4) 0 = not a problem 4 = Serious problem Translated to 0 to 100 scale, higher score indicate greater levels of distress
HADS: Hospital Anxiety and Depression Scale C‐DIRECT 2019	2 subscales of 7 items (0 to 3) 0 = no impairment 3 = severe impairment More than 8; presence of anxiety and depression More than 16 identifies caseness for the total scale
KDQoL‐SF: Kidney Disease Quality of Life‐Short Form C‐DIRECT 2019	43 items (1 to 5) 1 = not at all bothered 5 = extremely bothered Scores range from 0 to 100, higher score indicates better QoL
DDFQ: Dialysis Diet and Fluid Non‐Adherence Questionnaire C‐DIRECT 2019	Days not adherent in past 14 days Provides score for frequency Rating of their degree in which they deviated from guidelines (0 to 4) 0 = none 4 = very severe Lower scores suggest lower non‐adherence
SDSCA: Summary of Diabetes Self‐Care Activities C‐DIRECT 2019	6 subscales (0 to 7) Higher total and subscale score indicates better diabetes and self‐management over a week
DSES: Diabetes Self Efficacy Scale C‐DIRECT 2019	8 items (0 to 10) 0 = not at all confident 10 = totally confident Higher scores indicate higher self‐efficacy
HEIQ: Health Education Impact Questionnaire C‐DIRECT 2019	8 items (1 to 4) 1 = strongly disagree 4 = strongly disagree Higher scores indicate better outcomes
ADDQoL: Audit of Diabetes Dependent Quality of Life Steed 2005	13 domains, impact (‐3 to +3) and importance (0 to 3) Impact ‐3 = a great deal better 3 = great deal worse Importance 3 = very important 0 = Not at all important
Diabetes Self‐Management Knowledge McMurray 2002	12 domains, 53 items (multiple choice and true/false) Higher scores indicate better outcomes
Diabetes Self‐Care Behaviours Inventory McMurray 2002	6 domains Higher scores indicate better outcomes
PHQ: Patient Health Questionnaire Kopf 2012	8 domains (0 to 12) 0‐2 = normal 3‐5 = mild 6‐8 = moderate 9‐12 = severe Total score ≥ 3 for first 2 questions suggests anxiety Total score ≥ 3 for last 2 questions suggests depression Lower score better

Appendix 4. GRADE approach

The GRADE approach assesses the certainty of a body of evidence, rating it in one of four grades (GRADE 2008).

• High: we are very confident that the true effect lies close to that of the estimate of the effect

• Moderate: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of effect, but there is a possibility that it is substantially different

• Low: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect

• Very low: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of the effect.

We decreased the certainty of evidence if there was (GRADE 2011).

• Serious (‐1) or very serious (‐2) limitations in the study design or execution (risk of bias)

• Important inconsistency of results (‐1)

• Some (‐1) or major (‐2) uncertainty about the directness of evidence;

• Imprecise or sparse data (‐1) or serious imprecision (‐2)

• High probability of publication bias (‐1).

We increased the certainty of evidence if there was (GRADE 2011)

• A large magnitude of effect (direct evidence, relative risk (RR) = 2 – 5 or RR = 0.5 – 0.2 with no plausible confounders) (+1); very large with RR > 5 or RR < 0.2 and no serious problems with risk of bias or precision; more likely to rate up if the effect is rapid and out of keeping with prior trajectory; usually supported by indirect evidence (+2)

• Evidence of a dose‐response gradient (+1)

• All plausible residual confounders or biases would reduce a demonstrated effect or suggest a spurious effect when results show no effect (+1).

Data and analyses

Comparison 1. Educational programmes plus routine care versus routine care alone.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Death	4		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.1.1 Death (any cause)	4	424	Risk Ratio (M‐H, Random, 95% CI)	0.83 [0.31, 2.19]
1.1.2 DKD‐related death	1	110	Risk Ratio (M‐H, Random, 95% CI)	Not estimable
1.1.3 Cardiovascular disease‐related death	2	289	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.26, 2.73]
1.2 HbA1c [%]	4		Mean Difference (IV, Random, 95% CI)	‐0.42 [‐0.53, ‐0.31]
1.3 Attaining HbA1c < 6.5%	1	179	Risk Ratio (M‐H, Random, 95% CI)	2.43 [1.37, 4.32]
1.4 Kidney failure	1	110	Risk Ratio (M‐H, Random, 95% CI)	3.22 [0.13, 77.41]
1.5 Patient‐oriented measures: beliefs at the end of treatment (attitude scales)	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.5.1 Seriousness	1	99	Mean Difference (IV, Random, 95% CI)	0.09 [‐0.24, 0.42]
1.5.2 Treatment effectiveness	1	99	Mean Difference (IV, Random, 95% CI)	0.25 [0.07, 0.43]
1.5.3 Personal control	1	99	Mean Difference (IV, Random, 95% CI)	0.31 [‐0.03, 0.65]
1.6 Patient‐oriented measures: beliefs at the end of follow‐up (attitude scales)	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.6.1 Seriousness	1	99	Mean Difference (IV, Random, 95% CI)	0.11 [‐0.24, 0.46]
1.6.2 Treatment effectiveness	1	99	Mean Difference (IV, Random, 95% CI)	0.24 [‐0.00, 0.48]
1.6.3 Personal control	1	99	Mean Difference (IV, Random, 95% CI)	0.31 [0.01, 0.61]
1.7 Patient‐oriented measures: knowledge of diabetes at the end of treatment	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.7.1 Diagnosis	1	83	Mean Difference (IV, Random, 95% CI)	0.80 [0.54, 1.06]
1.7.2 Monitoring	1	83	Mean Difference (IV, Random, 95% CI)	1.30 [0.92, 1.68]
1.7.3 Hypoglycaemia	1	83	Mean Difference (IV, Random, 95% CI)	1.10 [0.81, 1.39]
1.7.4 Hyperglycaemia	1	83	Mean Difference (IV, Random, 95% CI)	0.50 [0.22, 0.78]
1.7.5 Medication: insulin	1	83	Mean Difference (IV, Random, 95% CI)	1.40 [0.90, 1.90]
1.7.6 Medication: oral	1	83	Mean Difference (IV, Random, 95% CI)	0.70 [0.38, 1.02]
1.7.7 Personal health habits	1	83	Mean Difference (IV, Random, 95% CI)	1.40 [1.06, 1.74]
1.7.8 Diet	1	83	Mean Difference (IV, Random, 95% CI)	0.40 [0.07, 0.73]
1.7.9 Exercise	1	83	Mean Difference (IV, Random, 95% CI)	0.80 [0.49, 1.11]
1.7.10 Chronic complications	1	83	Mean Difference (IV, Random, 95% CI)	0.90 [0.59, 1.21]
1.7.11 Living with diabetes and coping with stress	1	83	Mean Difference (IV, Random, 95% CI)	0.60 [0.21, 0.99]
1.8 Patient‐oriented measures: general knowledge of diabetes	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.8.1 At the end of treatment	1	97	Mean Difference (IV, Random, 95% CI)	15.82 [8.39, 23.25]
1.8.2 At the end of follow‐up	1	97	Mean Difference (IV, Random, 95% CI)	14.39 [7.45, 21.33]
1.9 Patient‐oriented measures: self‐efficacy at the end of treatment	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.9.1 Total	1	96	Mean Difference (IV, Random, 95% CI)	19.00 [12.58, 25.42]
1.9.2 Home blood glucose monitoring	1	79	Mean Difference (IV, Random, 95% CI)	6.96 [‐2.87, 16.79]
1.9.3 Diet	1	97	Mean Difference (IV, Random, 95% CI)	0.74 [‐7.51, 8.99]
1.9.4 Exercise	1	96	Mean Difference (IV, Random, 95% CI)	3.64 [‐7.04, 14.32]
1.10 Patient‐oriented measures: self‐efficacy at the end of follow‐up	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.10.1 Total	1	96	Mean Difference (IV, Random, 95% CI)	2.97 [‐3.43, 9.37]
1.10.2 Home blood glucose monitoring	1	79	Mean Difference (IV, Random, 95% CI)	11.28 [1.92, 20.64]
1.10.3 Diet	1	97	Mean Difference (IV, Random, 95% CI)	3.46 [‐4.32, 11.24]
1.10.4 Exercise	1	96	Mean Difference (IV, Random, 95% CI)	8.28 [‐2.04, 18.60]
1.10.5 Diabetes self‐efficacy scale total	1	44	Mean Difference (IV, Random, 95% CI)	‐0.57 [‐1.65, 0.51]
1.11 Patient‐oriented measures: self‐management behaviour changes at the end of treatment	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.11.1 Checking feet	1	83	Risk Ratio (M‐H, Random, 95% CI)	1.63 [1.01, 2.63]
1.11.2 Using lotion	1	83	Risk Ratio (M‐H, Random, 95% CI)	9.71 [2.45, 38.56]
1.11.3 Wearing appropriate shoes and socks	1	83	Risk Ratio (M‐H, Random, 95% CI)	4.39 [1.87, 10.32]
1.11.4 Blood glucose self‐monitoring	1	83	Risk Ratio (M‐H, Random, 95% CI)	1.20 [0.81, 1.79]
1.11.5 Carries carbohydrate	1	83	Risk Ratio (M‐H, Random, 95% CI)	1.90 [0.93, 3.87]
1.11.6 Eye examination	1	83	Risk Ratio (M‐H, Random, 95% CI)	1.48 [0.95, 2.29]
1.11.7 Stopped smoking	1	21	Risk Ratio (M‐H, Random, 95% CI)	0.81 [0.09, 7.58]
1.12 Patient‐oriented measures: behavioural changes at the end of treatment	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.12.1 Diet: general	1	100	Mean Difference (IV, Random, 95% CI)	0.73 [0.10, 1.36]
1.12.2 Diet: specific diet	1	100	Mean Difference (IV, Random, 95% CI)	1.02 [0.42, 1.62]
1.12.3 Exercise	1	100	Mean Difference (IV, Random, 95% CI)	0.76 [‐0.11, 1.63]
1.12.4 Home blood glucose monitoring	1	100	Mean Difference (IV, Random, 95% CI)	2.13 [1.18, 3.08]
1.12.5 Foot care	1	100	Mean Difference (IV, Random, 95% CI)	0.19 [‐0.72, 1.10]
1.13 Patient‐oriented measures: behavioural changes at the end of follow‐up	2		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.13.1 Diet: general	2	142	Mean Difference (IV, Random, 95% CI)	0.09 [‐0.46, 0.64]
1.13.2 Diet: specific diet	2	142	Mean Difference (IV, Random, 95% CI)	0.46 [‐0.02, 0.93]
1.13.3 Exercise	2	142	Mean Difference (IV, Random, 95% CI)	0.45 [‐0.28, 1.18]
1.13.4 Home blood glucose monitoring	2	142	Mean Difference (IV, Random, 95% CI)	0.62 [‐1.23, 2.48]
1.13.5 Foot care	2	142	Mean Difference (IV, Random, 95% CI)	0.06 [‐0.70, 0.83]
1.14 Estimated GFR [mL/min/1.73 m2]	1	179	Mean Difference (IV, Random, 95% CI)	0.46 [‐3.71, 4.63]
1.15 Urinary albumin‐creatinine ratio [mg/g]	1	179	Mean Difference (IV, Random, 95% CI)	0.35 [‐1.01, 1.71]
1.16 Blood pressure [mm Hg]	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.16.3 Systolic blood pressure	1	179	Mean Difference (IV, Random, 95% CI)	‐11.12 [‐16.38, ‐5.86]
1.16.4 Diastolic blood pressure	1	179	Mean Difference (IV, Random, 95% CI)	‐5.43 [‐9.12, ‐1.74]
1.17 Glycaemic events	1		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.17.1 Hypoglycaemia	1	179	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.67, 1.08]
1.17.2 Serious hypoglycaemia	1	179	Risk Ratio (M‐H, Random, 95% CI)	0.08 [0.00, 1.33]
1.18 Non‐fatal cardiovascular events	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
1.18.1 Total cardivascualar events	1	110	Risk Ratio (M‐H, Random, 95% CI)	1.25 [0.45, 3.49]
1.18.2 Stroke	2	289	Risk Ratio (M‐H, Random, 95% CI)	4.06 [0.45, 36.26]
1.18.3 Myocardial infarction	2	289	Risk Ratio (M‐H, Random, 95% CI)	1.02 [0.35, 2.96]
1.18.4 Heart failure	1	179	Risk Ratio (M‐H, Random, 95% CI)	1.98 [0.18, 21.42]
1.19 Quality of life	2		Std. Mean Difference (IV, Random, 95% CI)	Subtotals only
1.19.1 Patient Health Questionnaire (PHQ) stress score	1	103	Std. Mean Difference (IV, Random, 95% CI)	‐0.47 [‐0.86, ‐0.08]
1.19.2 KDQoL: physical composite summary	1	42	Std. Mean Difference (IV, Random, 95% CI)	0.17 [‐0.44, 0.77]
1.19.3 KDQoL: mental composite summary	1	42	Std. Mean Difference (IV, Random, 95% CI)	‐0.33 [‐0.94, 0.28]
1.19.4 KDQoL: kidney disease composite summary	1	42	Std. Mean Difference (IV, Random, 95% CI)	‐0.37 [‐0.99, 0.24]
1.19.5 KDQoL: general health composite summary	1	42	Std. Mean Difference (IV, Random, 95% CI)	‐0.08 [‐0.69, 0.53]
1.20 Lipids [mmol/L]	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
1.20.1 Total cholesterol	1	179	Mean Difference (IV, Random, 95% CI)	‐0.35 [‐0.63, ‐0.07]
1.20.2 HDL cholesterol	1	179	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.09, 0.03]
1.20.3 LDL cholesterol	1	179	Mean Difference (IV, Random, 95% CI)	‐0.40 [‐0.65, ‐0.14]
1.20.4 Triglycerides	1	179	Mean Difference (IV, Random, 95% CI)	0.07 [‐0.38, 0.52]
1.21 Adverse events: non‐fatal (including hypoglycaemic and CVD events)	1	179	Risk Ratio (M‐H, Random, 95% CI)	1.03 [0.89, 1.18]
1.22 Serious adverse events: emergency hospitalisation or death (including serious hypoglycaemic and CVD events)	2	289	Risk Ratio (M‐H, Random, 95% CI)	0.76 [0.36, 1.62]

Comparison 2. Multidisciplinary, multifactorial education programmes versus routine care.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 HbA1c [%]	1	120	Mean Difference (IV, Random, 95% CI)	‐0.40 [‐1.00, 0.20]
2.2 Kidney failure	1	120	Risk Ratio (M‐H, Random, 95% CI)	0.47 [0.22, 1.01]
2.3 Estimated GFR [mL/min/1.73 m2]	1	120	Mean Difference (IV, Random, 95% CI)	2.03 [‐3.44, 7.50]
2.4 Blood pressure [mm Hg]	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.4.1 Systolic blood pressure	1	120	Mean Difference (IV, Random, 95% CI)	‐0.19 [‐6.41, 6.03]
2.4.2 Diastolic blood pressure	1	120	Mean Difference (IV, Random, 95% CI)	‐3.40 [‐8.02, 1.22]
2.5 Glycaemic events	2		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
2.5.1 Hypoglycaemia	2	210	Risk Ratio (M‐H, Random, 95% CI)	0.57 [0.10, 3.36]
2.5.2 Hyperglycaemia	1	90	Risk Ratio (M‐H, Random, 95% CI)	0.14 [0.02, 1.11]
2.6 Lipids [mg/dL]	1		Mean Difference (IV, Random, 95% CI)	Subtotals only
2.6.1 HDL cholesterol	1	120	Mean Difference (IV, Random, 95% CI)	0.03 [‐4.39, 4.45]
2.6.2 LDL cholesterol	1	120	Mean Difference (IV, Random, 95% CI)	‐5.87 [‐20.11, 8.37]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

C‐DIRECT 2019.

Study characteristics
Methods	Study design Parallel RCT Study duration: not reported Follow‐up: 12 weeks Country: Singapore Setting: multicentre from participating dialysis centres of the National Kidney Foundation of Singapore
Participants	Study characteristics Inclusion criteria: > 21 years; coexisting DM and ESKD; on HD for a minimum of 3 months; HbA1c level ≥ 8% (at baseline); were able to communicate in English or Mandarin Exclusion criteria: serious physical or mental health conditions that would prevent or hinder study participation (consent and assessments); hospitalised; fluent only in Malay, Tamil or other dialects Baseline characteristics Number (randomised/analysed): intervention group (20/19); control group (24/23) Mean age ± SD (years): intervention group (61.8 ± 9.4); control group (63.3 ± 8.0) Sex (M/F): intervention group (12/8); control group (9/15)
Interventions	Intervention group (Education + self‐management) Combined Diabetes and Renal Control Trial (C‐DIRECT) intervention, a nurse‐led intervention based on motivational interview and self‐management The C‐DIRECT intervention consisted of three weekly chair‐side sessions delivered by diabetes specialist nurses The facilitators completed a 2‐day group training course to deliver the C‐DIRECT intervention followed by 2 sessions of one‐to‐one coaching. The training course consisted of 1‐day of self‐management principles (e.g. problem‐solving and goal‐setting) and 1‐day of motivational interviewing (key focus on elicit, provide‐elicit framework in reference to providing clinical feedback and advice). A MINT (Motivational Interviewing Network of Trainers) trainer observed facilitators for 2 pilot intervention sessions and coached/provided feedback as needed to ensure consistency of delivery and fidelity to behavioural change principles. The purpose of the sessions with patients was (a) to explore and expand understanding and activation around self‐management behaviours and (b) to collaboratively set goals to work towards more effective disease management. Self‐management strategies include goal setting, action planning, self‐monitoring, and feedback. The sessions were typically around 30 min Control group (usual care) Including regular blood tests and medical follow‐ups and care by a multidisciplinary team, including renal doctors, nurses, dietitians, exercise specialists, and medical social workers Co‐intervention HD sessions
Outcomes	Reported outcomes Primary outcomes Feasibility of recruitment: assessed at baseline and 12 weeks follow‐up. Feasibility was measured by the success of recruitment (% of consent to study; % of decline) and randomisation (% of consent to randomise; % drop out following randomisation) Retention: assessed at baseline and 12 weeks follow‐up. Retention was measured based on attendance of sessions, ability to gather data at the time points, whether questionnaires were completed (% completion /missing data), and delivery of the intervention Acceptability of the intervention: assessed at baseline and 12 weeks follow‐up. Acceptability was measured by drop‐out rates and qualitative interviews conducted at the end of the trial, assessed at baseline and 12 weeks follow‐up Secondary outcomes Efficacy to improve glycaemic control, assessed at baseline and 12 weeks follow‐up Adverse events (including death), assessed at baseline and 12 weeks follow‐up Distress (20‐item PAID scale): assessed at baseline and 12 weeks follow‐up Distress (7‐item HADS): assessed at baseline and 12 weeks follow‐up QoL (43‐item KDQoL‐SF): assessed at baseline and 12 weeks follow‐up Adherence and self‐care (DDFQ and SDSCA): assessed at baseline and 12 weeks follow‐up Sand self‐management skills (SDSCA): assessed at baseline and 12 weeks follow‐up Sand self‐management skills (DSES): assessed at baseline and 12 weeks follow‐up Sand self‐management skills (8‐domain HEIQ): assessed at baseline and 12 weeks follow‐up Biochemical markers (phosphate and potassium levels); protein catabolic rate, albumin, Hb and interdialytic weight gains: assessed at baseline and 12 weeks follow‐up
Notes	Additional information Funding: NKF Singapore Research Fund (NKFRC/2013/01/20)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Patients were randomised according to dialysis shifts." Quote: "Randomizing by shifts rather than dialysis centres can also potentially control for differences across centres (number of beds; layout of space, etc) that may introduce unforeseen bias across study arms. Block Randomisation was undertaken following baseline assessment, using a random number sequence produced by a computer‐generated program (randomizer.org)."
Allocation concealment (selection bias)	Unclear risk	Method of allocation concealment was not reported in sufficient detail to permit judgement
Blinding of participants and personnel (performance bias) All objective outcomes	Unclear risk	Quote: "Assessors that collected and analysed the data were independent to study care team and remained blind to study arm allocation by use of study codes. It was not possible to blind facilitators and patients as the intervention required input by these parties." Comment: an open‐label study is considered as high risk of bias. However, objective outcomes may not be influenced
Blinding of participants and personnel (performance bias) All subjective outcomes	High risk	Quote: "Assessors that collected and analysed the data were independent to study care team and remained blind to study arm allocation but use of study codes. It was not possible to blind facilitators and patients as the intervention required input by these parties." Comment: an open‐label study is considered high risk of bias
Blinding of outcome assessment (detection bias) All objective outcomes	Low risk	Quote: "Assessors that collected and analysed the data were independent to study care team and remained blind to study arm allocation but use of study code.". Comment: the objective outcomes wouldn't be influenced by blinding
Blinding of outcome assessment (detection bias) All subjective outcomes	Low risk	Quote: "Assessors that collected and analysed the data were independent to study care team and remained blind to study arm allocation but use of study code."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "Of the 44 recruited at baseline, 42 patients were evaluated at follow‐up." "All patients completed the three sessions of the program. At the conclusion of the study, the follow‐up questionnaire was completed by N= 42 (retention rate = 95.5%) of patients. One patient in the intervention discontinued the study due to health deterioration and prolonged hospitalisation and one patient in usual care died." Comment: 19/20 participants in the intervention group and 23/24 participants in the control group completed the study and were included in the analysis; < 5% loss to follow‐up. Reasons were provided and probably were not related to discontinuation. No imbalance between treatment groups was reported
Selective reporting (reporting bias)	High risk	Prespecified outcomes were reported. Some outcomes reported in the protocol were not reported. Clinically relevant outcomes that would be expected for this type of intervention were not reported
Other bias	Low risk	Quote: "The funding body was not involved in designing the study, collection, analysis, and interpretation of data, and in writing of the manuscript." Comment: similar baseline characteristics were reported between treatment groups. Funding did not influence data analysis and interpretation

Fogelfeld 2017.

Study characteristics
Methods	Study design Proof of concept RCT Study duration: 2007 to 2013 Follow‐up: 6 months and 2 years Country: USA Setting: single centre
Participants	Study characteristics Inclusion criteria: T2DM; 18 to 70 years; documented advanced diabetic nephropathy defined as impaired eGFR corresponding to CKD stages 3‐4 (eGFR > 15 mL/min and < 60 mL/min); presence of proteinuria or albuminuria (A: current presence of microalbuminuria; B: current presence of microalbuminuria and documentation of previous microalbuminuria; C: current presence of microalbuminuria and documentation of diabetic retinopathy or laser therapy; D: if only microalbuminuria and A, B, or C criteria is not fulfilled, then renal ultrasound should be done to demonstrate normal‐sized kidneys); cognitive functioning that allows self‐management of diabetes and hypertension control; fasting or random blood glucose < 400 mg/dL Exclusion criteria: T1DM; SCr > 4.0 mg/dL and/or eGFR of < 15 mL/min; onKRT; hyperkalaemia (potassium > 5.0 mEq/L); known renal artery stenosis; known cancer, hepatic impairment (such as hepatitis B or C), dementia or other chronic medical diseases such as but not limited to HIV, lupus, gammopathies and other chronic glomerular diseases; severe heart failure (NYHA Class III or IV symptoms and/or LVEF < 25%); valvular or outflow tract obstruction; significant physical and psychological disability that precludes regular attendance at clinics for follow‐up or self‐management ability of diabetes and hypertension; unable to speak or comprehend English; unwilling or unable to provide informed consent; pregnant or lactating women; current substance or alcohol abuse Baseline characteristics Number (randomised/analysed): intervention group (60/60); control group (60/60) Mean age ± SD (years): intervention group (56.27 ± 7.46;) control group (58.69 ± 7.46) Gender (males): intervention group (60%); control group (56.7%) Duration of diabetes: not reported Ethnicity (African‐American): intervention group (51.9%); control group (56.0%) Mean SBP/DBP ± SD (mm Hg): intervention group (141.8 ± 24.45/70.48 ± 13.48); control group (144.08 ± 23.11/73.15 ± 12.98) BMI ± SD (kg/m2): intervention group (male: 32.71 ± 6.12; female: 35.69 ± 8.72); control group (male: 33.86 ± 7.27; female: 35.27 ± 8.31) Mean SCr, range (mg/dL): intervention group (1.9, 1.6 to 2.5); control group (2.1, 1.6 to 2.5) Mean HbA1c ± SD (%): intervention group (8.19 ± 2.03); control group (8.38 ± 2.33) MEan eGFR ± SD (mL/min/1.73 m2): intervention group (37.95 ± 10.74); control group (37.18 ± 13.00) Mean UACR, range (mg/g): intervention group (853.4, 121 to 2461); control group (707.2, 180 to 1414) Co‐morbidities Not reported
Interventions	Intervention group (Multifactorial‐multidisciplinary intervention) Coordinated medical care combined with tight control of known renal risk factors, including BP, glycaemia, lipid control, and albuminuria. Group diet instruction is given based on the guidelines for managing diabetes and dyslipidaemia (American Diabetes Association, 2007) and renal disease (KDOQI 2007) This is followed by individual visits with the entire study staff (an endocrinologist, nephrologist, nurse practitioner, certified diabetes educator/dietitian, and research coordinator) to improve coordination of care and to integrate better each patient's various treatment protocols impacting the underlying CKD 3–4, including glycaemia, BP, albuminuria, hyperlipidaemia, hyperkalaemia, hyperphosphataemia, and hyperparathyroidism In addition to study visits, case management and additional follow‐ups were instituted as clinically necessary to promote target achievement The intervention visit frequency was monthly for the first 6 months and bimonthly for the next 18 months, for a total of 15 clinic visits over two years. These visits replaced their separate usual care visits to diabetes and renal clinics, typically quarterly or 16 visits over two years Patients may have unscheduled visits as deemed clinically necessary Patients assessed as needing more intensive follow‐up were also case‐managed with frequent phone contact by a study staff member Control group (usual care) Visits with primary care physicians and (for most participants) specialists in separate diabetes and renal clinics. The frequency of visits was determined by physicians in the relevant clinics Co‐interventions or additional treatments Quote: "No drug therapies beyond the usual formulary available to all CCHHS providers were introduced. Visit frequency allowed for more intensive diabetes management, including, when warranted, basal‐bolus multiple injection regimens and more complex hypertensive drug therapies using well‐defined escalation and safety protocols (see Supplementary materials). For dyslipidemia, conventional statin, fibrate, and niacin, medications were used". Duration of treatments and follow‐up details Over 2‐years, 6‐month treatments, or until reaching ESKD Quote: "At six‐month intervals during this 2‐year study, laboratory data were collected and physical exams performed on both intervention and control patients and included vitals and history taking (adverse events, review and adherence to medications, and use of contraindicated medications and supplements). Patients who reached the ESRD endpoint did not continue the study. For study dropouts, last observation data points were included and carried forward in data analysis".
Outcomes	Reported outcomes Development of ESKD: eGFR < 15 mL/min/1.73 m2 that persists in subsequent tests BP: < 130/80 mm Hg Glycaemia: HbA1c < 7% Lipids: LDL < 100 mg/dL; triglycerides < 150 mg/dL; HDL > 40 and 50 mg/dL for males and females Albuminuria Hypoglycaemia Hyperkalaemia Adverse events Review and adherence to medications Use of contraindicated medications and supplements Reduction of proteinuria < 0.5 g/day
Notes	Additional information A priori‐published protocol: not reported Conflicts of interest/disclosures: "The authors have nothing to disclose" Funding: "The study was supported in part as an investigator initiated trial by Sanofi"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The ... study was a stratified randomized controlled trial" Quote: "Patients were randomized into eGFR striatae based on baseline estimated eGFRs, calculated using MDRD equation (Levey et al., 2006)" Comment: limited information is provided on the details of how the randomisation method was undertaken
Allocation concealment (selection bias)	Unclear risk	Comment: No information provided regarding concealment of allocation of groups
Blinding of participants and personnel (performance bias) All objective outcomes	Low risk	Quote: "The study did not allow for blinding" Comment: no mention of blinding or blinding details for the participants' or personnel. This study would have been hard to blind participants and personal and adequately conceal what group they are in. The objective outcomes reported probably would not change due to blinding
Blinding of participants and personnel (performance bias) All subjective outcomes	High risk	Quote: "The study did not allow for blinding" Comment: no mention of blinding or blinding details for the participants or personnel. The study did not plan to blind anyone. This may introduce potential bias for any of the self‐reported outcomes
Blinding of outcome assessment (detection bias) All objective outcomes	Low risk	Quote: "The study did not allow for blinding" Comment: no mention of blinding or blinding details for the outcome assessors. Due to the design of the study, it was open‐label. The objective outcomes reported in this study would probably not be influenced by lack of blinding, and knowledge of the assigned intervention would not impact the outcome measures
Blinding of outcome assessment (detection bias) All subjective outcomes	High risk	Quote: "The study did not allow for blinding" Comment: no mention of blinding details for the outcome assessors. The subjective outcomes reported could be influenced by lack of blinding, and knowledge of the assigned intervention could impact the outcome measures
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Comment: all participants were accounted for from start to end of the trial. Attrition rates were low to moderate in each group: multifactorial education intervention group (23%); usual care control group (12%)
Selective reporting (reporting bias)	Unclear risk	Comment: all planned outcomes in the methods were reported in the results; no access to a priori published protocol
Other bias	High risk	Conflicts of interest/disclosures: "The authors have nothing to disclose". "No other potential conflicts of interest relevant to this article were reported" Funding: "The study was supported in part as an investigator initiated trial by Sanofi" Comment: pharmaceutical industry funding

Guo 2022.

Study characteristics
Methods	Study design Parallel RCT Study duration: January 2020 to January 2021 Follow‐up: 12 weeks Country: China Setting: Single centre
Participants	Study characteristics Inclusion criteria: met the diagnostic criteria of DKD in the uraemic phase (history of diabetes and 3 times of urine protein examinations in 3 consecutive months with the urinary excretion > 20 to 300 μg/min while other causes of increased urinary protein excretion were excluded; clinical symptoms included frequent urination, foamy urine, dizziness, nausea, vomiting, and oedema of the lower limbs.; good compliance; did not take any medication such as vitamins or ACEi in recent 1 month Exclusion criteria: acute heart failure; allergic to alogliptin; pregnant or lactating; malignant tumours Baseline characteristics Number: intervention group (45); control group (45) Mean age ± SD (years): intervention group (59.89 ± 10.53); control group (60.91 ± 9.33) Gender (M/F): intervention group (25/20); control group (27/18) Duration of diabetes: not reported Mean SBP/DBP ± SD (mm Hg): intervention group (141.8 ± 24.45/70.48 ± 13.48); control group (144.08 ± 23.11/73.15 ± 12.98) BMI (kg/m2): intervention group (20.70 ± 3.16); control group (21.14 ± 2.54) Smoker (yes): intervention group (19); control group (17) Co‐morbidities Not reported
Interventions	Intervention group (multifactorial‐multidisciplinary intervention) The combined group was given systematic diet education combined with multidisciplinary nursing on the basis of medication treatment The systematic diet education group included an endocrinologist, a nutritionist, a specialist nurse, and three nurses, headed by a specialist nurse The group leader conducted systematic dietary education on Saturday from 9:00 to 11:00, including the causes of DKD in the uraemic phase, treatment methods, healthy diet, and personal life management in the form of video, pictures, and text, to popularise disease‐related knowledge, improve awareness of healthy diet and life, and enhance self‐management ability. After the course, the nutritionist was responsible for answering patients' nutrition management questions. The nutrition management team closely monitored the vital signs of patients and jointly discussed and formulated the diet plan. The multidisciplinary nursing team consisted of an endocrinologist in charge of diabetes treatment, two nurses from the dialysis department in charge of comprehensive care, a nutritionist in charge of the daily diet for patients, and a psychological consultant in charge of daily psychological guidance Regular treatment and psychological counselling were performed by the multidisciplinary team to timely solve the treatment, nursing, psychological, and other problems for patients Control group(usual care) The conventional groups were treated with conventional nursing intervention after medication treatment, including medication guidance, exercise guidance, and self‐observation Co‐interventions or additional treatments All patients were treated with alogliptin. Patients orally took 25 mg/time of alogliptin (manufacturer: Japan Takeda Pharmaceutical Co., Ltd.; NMPA Approval No. H20130548; specification: 25 mg x 10 s) once/day for 12 continuous weeks Duration of treatments and follow‐up details Over 2 years, 6‐month treatments, or until reaching E
Outcomes	Reported outcomes Nutrition status and levels of calcium and phosphorus metabolism Serum albumin, total protein, serum prealbumin Compliance SAS Hypoglycaemia and hyperglycaemia
Notes	Additional information Funding: "The authors received no financial support for the research, authorship, and/or publication of this article."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "The subjects were divided into combined group and routine group by random number table method." Comment: details not reported
Allocation concealment (selection bias)	Unclear risk	Insufficient information to permit judgement
Blinding of participants and personnel (performance bias) All objective outcomes	Unclear risk	Blinding of outcomes assessors not reported
Blinding of participants and personnel (performance bias) All subjective outcomes	High risk	Open‐label study; blinding of outcomes assessors not reported
Blinding of outcome assessment (detection bias) All objective outcomes	Unclear risk	Blinding of outcomes assessors not reported
Blinding of outcome assessment (detection bias) All subjective outcomes	High risk	Open‐label study; blinding of outcomes assessors not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: all participants were accounted for from start to end of the trial
Selective reporting (reporting bias)	Unclear risk	Insufficient information to permit judgement
Other bias	Unclear risk	Insufficient information to permit judgement

Kopf 2012.

Study characteristics
Methods	Study design Parallel RCT Study duration: designed as a 5‐year study Follow‐up: 8 weeks 1, 2 and 3 years Country: Germany Setting: single centre
Participants	Study characteristics Inclusion criteria: T2DM; albuminuria (> 20 mg/L in two separate spot urines); 30 to 70 years; documented history of microalbuminuria in at least 2 separate urine samples (albumin‐excretion > 30 mg/24 h or > 20 mg/L) Exclusion Criteria: diabetes duration <3 years; pre‐existing non‐diabetic kidney disease; psychiatric disorders; alcohol or drug abuse; malignant tumours or haematologic disorders; heart failure (NYHA III‐IV); acute coronary syndrome; healthy volunteers Baseline Characteristics Number: intervention group (53); control group (57) Mean age ± SD (years): intervention group (58.7 ± 7.4); control group (59.3 ± 7.8) Gender: (males): intervention group (70.2%); control group (80.7%) Mean BMI ± SE (kg/m2): intervention group (34.3 ± 7.1); control group (32.4 ± 4.8) Mean SCr ± SE (mg/dl): intervention group (0.92 ± 0.34); control group (0.85 ± 0.2) HbA1c (%): intervention group (7.26 ± 1.08); control group (7.27 ± 1.06) Mean eGFR ± SE (mL/min/1.73 m2): intervention group (87.1 ± 19.6); control group (90.7 ± 21.1) Mean UAE, range (mg/24 hours): intervention group (59.6, 18.9 to 171.4); control group (45.0, 25.6 to 105.3) Co‐morbidities (intervention group/control group) History of retinopathy (22.6%/26.3%); neuropathy (37.7%/56.1%); hypertension (86.8%/91.2%); myocardial infarction (22.0%/4.26%); peripheral artery occlusive disease (9.4%/14.0%); stroke (5.7%/7.0%)
Interventions	Intervention (Mindfulness‐based stress reduction intervention) 8‐week programme based on body and meditation practices that aim to increase openness, awareness and acceptance of all internal and external experiences Adapted to include practices for difficult thoughts and feelings related to diabetes Participants met once weekly in groups of 6–10 and for a booster session after 6 months The groups were led by a psychologist and a resident in internal medicine Control (Standard care) According to diabetes guidelines in both arms, all patients were seen regularly by a physician in our outpatient clinic to guarantee standardised medical treatment as usual. Co‐interventions or additional treatments None reported
Outcomes	Reported outcomes Albuminuria HbA1c (%) SBP and DBP (mm Hg) Psychiatric comorbidity: depression, stress Subjective health status (SF‐12): mental and physical
Notes	Additional information A priori‐published protocol: no protocol. Supplementary material provides further details (doi:10.1007/s00592‐013‐0542‐2) Conflicts of interest/disclosures: "None". Funding: "This study was supported by the Manfred Lautenschläger Foundation and Dietmar Hopp Foundation (both to P. Nawroth) and the Deutsches Zentrum für Diabetesforschund (DZD) in cooperation with the Institute for Diabetes Research and Metabolic Diseases (to H‐U. Häring, University of Tübingen, Germany). The Manfred Lautenschläger Foundation is a privately sourced foundation for this project. The funding was used to support physicians and study nurses as well as laboratory materials. The Dietmar Hopp Foundation is a privately sourced foundation supporting part of this study with laboratory materials. The Deutsches Zentrum für Diabetesforschung is funded by the Federal Ministry of Education and Research (BMBF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." Comment: 9 patients in the intervention group did not attend the training sessions as required (less than 5 sessions). Therefore, a per‐protocol analysis was performed at 12 months. For the intervention group, 52 were included in the ITT analysis, and 43 were included in the per‐protocol analysis at 12 months. At 3 years, 7 dropped out (lost interest) in the control group vs. 3 lost interest in the intervention group
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Participants were randomly assigned to one of the 2 groups in a 1:1 ratio"
Allocation concealment (selection bias)	Unclear risk	Comment: no information provided
Blinding of participants and personnel (performance bias) All objective outcomes	Low risk	Comment: open‐label study. The objective outcomes reported are not likely to be influenced by lack of blinding. It is unlikely that knowledge of the assigned intervention from participants and personnel would impact the outcome measures
Blinding of participants and personnel (performance bias) All subjective outcomes	High risk	Comment: open‐label study. The subjective outcomes reported could be influenced by lack of blinding, and knowledge of the assigned intervention could impact the outcome measures. For example, QoL, which is self‐reported
Blinding of outcome assessment (detection bias) All objective outcomes	Low risk	Comment: open‐label study. Even though this was open‐label, it is unlikely that knowledge of the assigned intervention from outcomes assessors would impact the outcome measures
Blinding of outcome assessment (detection bias) All subjective outcomes	High risk	Comment: open‐label study. The subjective outcomes reported could be influenced by lack of blinding, and knowledge of the assigned intervention could impact the outcome measures, for example, QoL, which is self‐reported. It is unclear what the role of the outcome assessors was for this
Incomplete outcome data (attrition bias) All outcomes	High risk	Comment: loss‐to‐follow‐up at 12 months was 1 intervention and 6 in control groups (reasons not provided) Comment: higher proportion of patients with a history of MI in the intervention group compared to the control group at baseline (22.0% vs. 4.26%) Comment: 9 patients in the intervention group did not attend the training sessions as required (less than 5 sessions). Therefore, a per‐protocol analysis was performed at 12 months. For the intervention group, 52 were included in the ITT analysis, and 43 were included in the per‐protocol analysis at 12 months. At 3 years, 7 dropped out (lost interest) in the control group vs. 3 lost interest in the intervention group
Selective reporting (reporting bias)	Unclear risk	Comment: results missing for outcomes recorded at baseline (the anxiety and eating disorder components of the PHQ) A priori‐published protocol: No protocol. Supplementary material provides further details (doi:10.1007/s00592‐013‐0542‐2)
Other bias	Unclear risk	Comment: possible selection bias for outcome, myocardial Infarction had a significant imbalance at baseline (intervention= 11 (22%); control= 2 (4.26%). Conflicts of interest/disclosures: "None". Funding: "This study was supported by the Manfred Lautenschläger Foundation and Dietmar Hopp Foundation (both to P. Nawroth) and the Deutsches Zentrum für Diabetesforschund (DZD) in cooperation with the Institute for Diabetes Research and Metabolic Diseases (to H‐U. Häring, University of Tübingen, Germany). The Manfred Lautenschläger Foundation is a privately sourced foundation to this project. The funding was used to support physicians and study nurses as well as laboratory materials. The Dietmar Hopp Foundation is a privately sourced foundation supporting part of this study with laboratory materials. The Deutsches Zentrum für Diabetesforschung is funded by the Federal Ministry of Education and Research (BMBF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

McMurray 2002.

Study characteristics
Methods	Study design Parallel RCT Study duration: not reported Follow‐up: 6, 9 and 12 months Country: USA Centre: multicentre (2 sites)
Participants	Study characteristics Inclusion criteria: ESKD requiring KRT with either HD or PD in combination with a T1DM or T2DM diagnosis Exclusion criteria: not reported Baseline characteristics Number: intervention group (45); control group (38) Mean age ± SD (years): intervention group (63.0 ± 13.5); control group (60.9 ± 11.7) Gender (M/F): intervention group (24/21); control group (21/17) Mean duration of diabetes ± SD (years): intervention group (20.5 ± 13.0); control group (22.0 ± 11.7) Months on KRT ± SD: intervention group (32.4 ± 22.8); control group (33.2 ± 11.7) Dialysis type (HD/PD): intervention group (37/8); control group (33/5) Co‐morbidities None reported other than diabetes
Interventions	Intervention group (education + routine treatment) Education programme content: self‐management education; diabetes care monitoring and management; motivational coaching Provider: diabetes care manager (and renal dietitian) Modality: face‐to‐face, one‐on‐one with the patient Routine treatment: glycaemic control, antihypertensive drugs, weight‐maintaining diet, dialysis Control group (routine treatment) Glycaemic control, antihypertensive drugs, weight‐maintaining diet, dialysis Co‐interventions or additional treatments None reported Duration of interventions Intervention was over 12 months
Outcomes	Reported outcomes Diabetes QoL (Diabetes form 2.1) Self‐knowledge Self‐management behaviours Glycaemic control (HbA1c%) Foot care Overall death
Notes	Additional information A priori published protocol: not reported, unable to locate online Conflicts of interest/disclosures: not reported Funding: "Supported in part by the Renal Care Group and a grant from The Kidney Foundation of Indiana".
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Quote: "Patients meeting inclusion criteria were randomly assigned to control or study groups. At the Jefferson unit, randomization occurred by assigning patients who underwent HD Monday, Wednesday, and Friday to the study group and Tuesday, Thursday, and Saturday to the control group. At the Marion unit, the reverse schedule was used for randomization. Patients undergoing PD were numerically randomized" Comment: the study states that it was randomised, but no details of the randomisation sequence are provided. Furthermore, patients were randomised according to the day of the week that they underwent surgery (the justification being allocation concealment). For PD patients, insufficient detail was provided, but they were said to be "numerically randomized." Quote: "Because the HD treatment environment is a close‐knit one, separation of the control and study groups by treatment days was chosen in hopes of reducing knowledge diffusion and discussion among patients between the two groups. It also was important to remove any physician biases" Quote: "Because the HD treatment environment is a close‐knit one, separation of the control and study groups by treatment days was chosen in hopes of reducing knowledge diffusion and discussion among patients between the two groups. It also was important to remove any physician biases" Quote: "Patients undergoing PD were numerically randomized"
Allocation concealment (selection bias)	Unclear risk	Quote: "Because the HD treatment environment is a close‐knit one, separation of the control and study groups by treatment days was chosen in hopes of reducing knowledge diffusion and discussion among patients between the two groups. It also was important to remove any physician biases" Comment: no information about allocation concealment methods was described. Separation of the control and study groups by treatment days may have helped conceal which treatment groups they were in, but this is unclear
Blinding of participants and personnel (performance bias) All objective outcomes	Low risk	Quote: "Because the HD treatment environment is a close‐knit one, separation of the control and study groups by treatment days was chosen in hopes of reducing knowledge diffusion and discussion among patients between the two groups. It also was important to remove any physician biases. Physicians in the dialysis facility cared for patients in either the study group or control group. There was no crossover of physician care" Comment: it appears that participants were blinded to treatment groups
Blinding of participants and personnel (performance bias) All subjective outcomes	Low risk	Comment: appears that participants were blinded to treatment groups
Blinding of outcome assessment (detection bias) All objective outcomes	Low risk	Quote: "Physicians in the dialysis facility cared for patients in either the study group or control group. There was no crossover of physician care." Comment: somewhat unclear description of whether the physicians were blinded. Very unclear if other outcomes assessors were blinded
Blinding of outcome assessment (detection bias) All subjective outcomes	High risk	Quote: "Physicians in the dialysis facility cared for patients in either the study group or control group. There was no crossover of physician care." Comment: unclear description of whether the physicians were blinded and other outcomes assessors. The subjective outcomes reported could be influenced by lack of blinding, and knowledge of the assigned intervention could impact the outcome measures
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: no loss to follow‐up
Selective reporting (reporting bias)	Unclear risk	Comment: all outcomes planned in the methods were reported in the results; clinically important outcomes were unstated, such as CV disease incidence. There was no a priori protocol or trial registration. Trial registration: not reported, unable to locate online
Other bias	Unclear risk	Comment: conflicts of interest or disclosures are not reported

MEMO 2011.

Study characteristics
Methods	Study design Parallel RCT Study duration: September 2006 to April 2007 Follow‐up: 4 years Country: UK Setting: multicentre (referred from primary care and specialist diabetes clinics)
Participants	Study information Inclusion criteria: confirmed diagnosis of T2DM and microalbuminuria confirmed overt proteinuria with a SCr < 180 µmol/L Exclusion criteria: history of malignancy or chronic liver disease; life expectancy < 5 years; learning disability, mental incapacity or immobility which precluded them from attending educational sessions; SCr >180 µmol/L or if participating in another research study Baseline characteristics Number: intervention group (94); control group (95) Mean age ± SD (years): intervention group (62.6 ± 10.3); control group (60.3 ± 10.7) Gender (males): intervention group (75.5%); control group (75.8%) Mean duration of diabetes ± SD (years): intervention group (11.0 ± 9.3); control group (11.9 ± 9.4) Ethnicity (White European/South Asian): intervention group (72.3%/23.4%); control group (64.2%/31.6%) Mean SBP/DBP ± SD (mm Hg): intervention group (139 ± 16/76 ± 12); control group (136 ± 16/77 ± 12) Mean bodyweight ± SD (kg): intervention group (93.9 ± 20.1); control group (93.6 ± 25.6) Mean BMI ± SD (kg/m2): intervention group (33.1 ± 6.8); control group (32.8 ± 7.9) Smoker (yes): intervention group (13.8%); control group (11.6%) Mean HbA1c ± SD (%, mmol/mol): intervention group (7.9 ± 1.4/63 ± 8); control group (8.0 ± 1.6/64 ± 6) Mean eGFR ± SD (mL/min/1.73 m2): intervention group (66.3 ± 14.7); control group (72.0 ± 19.8) Median UACR, IQR: intervention group (7.6, 2.8 to 18.8); control group (5.8, 3.2 to 17.6) Co‐morbidities (mean ± SD) Ischaemic heart disease: intervention group (24 ± 25.5); control group (14 ± 14.7) Congestive cardiac failure: intervention group (8 ± 8.5; control group (7 ± 7.4) Cerebrovascular accident: intervention group (10 ± 10.6); control group (5 ± 5.3) Peripheral vascular disease: intervention group (4 ± 4.3); control group (6 ± 6.3)
Interventions	Intervention group (self‐management & patient education) Structured self‐management education programme (including individual and group sessions) based on the DESMOND model and tailored to a multi‐ethnic population The programme focused on medication adherence and management of microalbuminuria and T2DM Participants were followed up every three months on a ‘‘one‐to‐one’’ basis Lifestyle changes, physical activity, medication adherence, and medication self‐titration were discussed and recorded in the participants' record books, providing general information on T2DM, healthy eating, physical activity, and exercise Structured education was based on the DESMOND model of patient education The educational programmes' content was underpinned by an empowerment philosophy and sound theoretical principles of adult learning The educational programme was delivered by trained DESMOND educators who are part of ongoing quality assurance and professional development programme Control group (usual care) According to local guidelines, the control group received standard care from their own clinician, consistent with NICE guidance on the management of individuals with T2DM and diabetic nephropathy. It also provides additional information on the management of individuals with T2DM of South Asian ethnicity Participants in the control group were not seen or treated by the study physician/team and had usual access to education provided as part of standard diabetes care in either primary or secondary care Co‐interventions or additional treatments None reported Duration of treatments The intensive intervention was delivered for 18 months Participants in both groups were followed up at 3 monthly intervals, and Education Medication Optimisation group participants were followed up on a ‘‘one‐to‐one’’ basis.
Outcomes	Reported outcomes HbA1c: mean change at 18 months BP: mean change Lipids (mean change): LDL; HDL; total cholesterol UACR: mean change Proportion of individuals reaching glycaemic targets (HbA1c ≤ 6.5%) Proportion of individuals reaching BP targets (≤ 130/70 mm Hg) Proportion of individuals reaching lipid targets (total cholesterol ≤ 3.5mmol/L; LDL ≤ 2.0mmol/L; or 30% reduction below baseline lipid levels) Modelled CVD risk scores Adverse events Serious adverse event
Notes	Additional information A priori‐published protocol: none reported Conflicts of interest/disclosures: "The authors declare that they have no conflict of interest". Funding: "The MEMO study was funded by a fellowship grant provided by Kidney Research, UK. The study is supported by the NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRC) for Leicestershire, Northamptonshire & Rutland, University Hospitals of Leicester".
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: no information provided regarding random sequence generation methods
Allocation concealment (selection bias)	Unclear risk	Comment: method of concealment not adequately described
Blinding of participants and personnel (performance bias) All objective outcomes	Low risk	Comment: the study was not blinded. The objective outcomes reported probably would not be influenced by blinding. This study would also be hard to adequately blind participants without knowing what group they are in
Blinding of participants and personnel (performance bias) All subjective outcomes	High risk	Quote: "Data on adverse events, serious adverse events or relevant clinical outcomes were obtained by self‐report and from letters of primary care physicians, specialist clinic letters or hospital discharge summaries" Comment: the study was not blinded. Some outcomes were subjective, for example, hypoglycaemia, which was self‐reported, and could be influenced by lack of blinding
Blinding of outcome assessment (detection bias) All objective outcomes	Low risk	Quote: "Data was recorded separately and assessed independently by a research physician who was not aware of the study participant’s treatment allocation and was not involved with any aspect of the study" Quote: "Biomedical measures in both groups were obtained at baseline, 6, 12 and 18 months under standard operating procedures, by a trained research assistant who was blinded to the participant’s treatment assignment and independent of the study team."
Blinding of outcome assessment (detection bias) All subjective outcomes	Low risk	Quote: "Data was recorded separately and assessed independently by a research physician who was not aware of the study participant’s treatment allocation and was not involved with any aspect of the study"
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: all participants were accounted for from the start to the end of the trial. Flow chart provides reasons for dropouts or withdrawals. Attrition rate was low (< 10% in each arm)
Selective reporting (reporting bias)	Unclear risk	Comment: all outcomes planned in the methods are reported in the results. No protocol has been published. Trial registration provided
Other bias	Unclear risk	Comment: potential selection bias due to some participants being recruited from specialist clinic settings (i.e. receiving more intensive treatment). Sub‐analysis of these participants was not provided Conflicts of interest/disclosures: "The authors declare that they have no conflict of interest" Funding: "The MEMO study was funded by a fellowship grant provided by Kidney Research, UK. The study is supported by the NIHR Collaborations for Leadership in Applied Health Research and Care (CLAHRC) for Leicestershire, Northamptonshire & Rutland, University Hospitals of Leicester"

MESMI 2010.

Study characteristics
Methods	Study design Parallel RCT Study duration: 2008 to 2009 Follow‐up: 3, 6 and 9 months Country: Australia Setting: single centre
Participants	Study characteristics Inclusion criteria: > 18 years; English speaking; mentally competent (Abbreviated Mental Health test); T1DM or T2DM and CKD (eGFR >15 and < 60 mL/min/ 1.73 m2) or DKD (microalbumin/creatinine ratios > 2.0 mg/mmol for men, > 3.5 mg/mmol for women); SBP >130 mm Hg treated with prescribed antihypertensive medication Exclusion criteria: lived more than 50 km from the city centre; pregnant; received a new diagnosis of cancer Baseline characteristics Number: intervention group (39); control group (41) Mean age ± SD (years): intervention (68 ± 8.3); control group (66 ± 10.8) Gender (M/F): intervention group (22/17); control group (23/18) Born outside of Australia: intervention group (25); control group (26) Mean BMI ± SD (kg/m2): intervention group (31.8 ± 5.4); control group (31.4 ± 5.9) Smoker (yes): intervention group (10); control group (10) Median SCr, IQR (µmol/L): intervention group (160, 120 to 200); control group (130.5, 107 to 16.5) Median HbA1c, IQR (%): intervention group (7.5, 6 to 8); control group (7.5, 7 to 8.5) Median eGFR, IQR (mL/min/1.73 m2): intervention group (35.5, 28 to 46); control group (45.5, 34 to 52) Co‐morbidities (mean ± SD): intervention group (7.7 ± 2.5; control group (8.2 ± 2.5)
Interventions	Intervention group (multifactorial, including education) Multifactorial intervention: self‐monitoring of BPe, individualised medication review, 20‐minute DVD, and fortnightly motivational interviewing follow‐up telephone contact for 12 weeks (to support blood pressure control and optimal medication self‐management) Delivered by an intervention nurse with renal specialist and doctoral qualifications and trained in motivational interview using a checklist and standing script for fidelity purposes Participants in the intervention group were taught how to take their BP, which involved being seated every morning after breakfast and taking their medications using their non‐dominant arm with an A&D Medical Pty. Ltd digital BP monitor supplied for the study (Model UA‐787, Saitama, Japan) Participants recorded their daily BP for approximately 3 months in a specific booklet issued for this purpose The individualised medication review involved the intervention nurse drawing up a chart of the participant’s prescribed medications that included the generic name of the medication, what the medication was for, the dose and when to take it, and targets for which to aim The 20‐min DVD involved an interactive, psychosocial approach to motivating people to take their medications, appealing to knowledge, thoughts and feelings, underpinned by the modified Health Belief Model Control group (usual care) Received standard care offered to patients with co‐existing diabetes and CKD, attending diabetes and nephrology outpatients’ clinics at the hospital BP control was the most important aspect of standard care, and care depended on the patient’s individual circumstances and morbidity Data were collected from the control group at the same time points as the intervention group Co‐interventions or additional treatments None reported Duration of treatments Fortnightly motivational interviewing telephone calls commenced 2 weeks after the intervention home visit, and continued fortnightly until follow‐up at 3‐months post enrolment
Outcomes	Reported outcomes BP (control): 3, 6, 9 months Medication adherence: pill counting per visit eGFR: 3, 6, 9 months SCr: 3, 6, 9 months HbA1c: 3, 6, 9 months
Notes	Additional information The study was conducted according to the protocol and under ethical guidelines of the National Health and Medical Research Council of Australia (National Health and Medical Research Council 2007) A priori published protocol: published Conflicts of interest/disclosures: "No conflict of interest has been declared by the authors". Funding: "This research was supported by an Australian Research Council (Linkage) Grant (LP0774989), Sigma Theta Tau International Small Grant, Nurses Memorial Centre Australian Legion of Ex‐ Ex‐Servicemen and Women Scholarship, and the Mona Menzies Nurses Board of Victoria Grant" Original inclusion criteria was modified Quote: "We had to modify our original inclusion criteria to improve the rate of recruitment because of difficulties obtaining standard information across diabetes and nephrology patients’ medical records. For example, some patients did not have microalbumin/creatinine ratios taken as part of routine care, and we reduced the presence of systolic hypertension for the previous clinic visit rather than the previous two clinic visits".
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Following recruitment, participants were allocated code numbers prior to enrolment and being randomised to the intervention or control group (1:1 ratio) by an off‐site statistician. A stratified block randomisation was conducted according to gender, age and systolic blood pressure (£140 vs >140 mmHg) recorded at recruitment"
Allocation concealment (selection bias)	Low risk	Quote: "People collecting data and assessing outcomes were blinded to group assignment." Quote: "The research assistant was trained to collect data and was blinded to group assignment" Quote: "The identity of all participants who were enrolled and randomised to receive the intervention was kept in a locked cabinet in the chief researcher’s office" Quote: "Following recruitment, participants were allocated code numbers prior to enrolment and being randomised to the intervention or control group (1:1 ratio) by an off‐site statistician"
Blinding of participants and personnel (performance bias) All objective outcomes	Low risk	Quote: "Participants in the intervention group could not be blinded and were asked to not disclose their group allocation to the research assistant during data collection" Comment: not possible to blind participants and personnel to behavioural treatment care. It is unlikely that blinding would effect the objective outcomes reported
Blinding of participants and personnel (performance bias) All subjective outcomes	High risk	Quote: "Participants in the intervention group could not be blinded and were asked to not disclose their group allocation to the research assistant during data collection" Comment: not possible to blind participants and personnel to behavioural treatment care. The subjective outcomes reported, such as blood pressure, which was reported daily by patients, could be influenced by blinding
Blinding of outcome assessment (detection bias) All objective outcomes	Low risk	Quote: "People collecting data and assessing outcomes were blinded to group assignment."Quote: "The research assistant was trained to collect data and was blinded to group assignment" Comment: study personnel and outcome assessors were blinded
Blinding of outcome assessment (detection bias) All subjective outcomes	Low risk	Quote: "People collecting data and assessing outcomes were blinded to group assignment."Quote: "The research assistant was trained to collect data and was blinded to group assignment" Comment: study personnel and outcome assessors were blinded
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment: all participants were accounted for from start to end of the trial. Attrition rates were low: education (7.7%), usual care (4.8%) Quote: "The results show a constant improvement in eGFR and serum creatinine (measures of kidney function) in both groups. It is important to mention that not all participants had their blood test results included in this study because tests conducted in primary care were not always recorded in the participant’s hospital medical history" Comment: unclear how this impacts final results; potentially doesn't matter as we recalculated ITT according to Cochrane Handbook using Case Available Analysis (dichotomous data) or Last Observation Carried Forward (continuous data)
Selective reporting (reporting bias)	Low risk	Comment: all outcomes planned in the methods were reported in the results. Trial registration and a priori‐published protocol were reported (matching). Some data represented in graphical form, unable to extract A priori published protocol: published
Other bias	Unclear risk	Comment: no pharmaceutical industry funding, and authors are clear of conflicts of interest Conflicts of Interests/Disclosures: "No conflict of interest has been declared by the authors" Funding declared: "This research was supported by an Australian Research Council (Linkage) Grant (LP0774989), Sigma Theta Tau International Small Grant, Nurses Memorial Centre Australian Legion of Ex‐ Servicemen and Women Scholarship, and the Mona Menzies Nurses Board of Victoria Grant" Comment: possible selection bias? Patients who lived more than 50km from Melbourne city centre were excluded Quote: "Over the duration of the study, participants in both groups were made more aware of their high blood pressure taken during data collection in the home, and changes to antihypertensive medications were common in both groups as a result of regular medical consultations. Additionally, the research assistant administered all survey questions that may have incurred a positive response bias" Comment: potential positive response bias Quote: "We had to modify our original inclusion criteria to improve the rate of recruitment because of difficulties obtaining standard information across diabetes and nephrology patients’ medical records. For example, some patients did not have microalbumin/creatinine ratios taken as part of routine care, and we reduced the presence of systolic hypertension for the previous clinic visit rather than the previous two clinic visits" Comment: orginal inclusion criteria was modified after the study had started. Possibly an issue with study design rather than bias?

Steed 2005.

Study characteristics
Methods	Study design Parallel RCT Study duration: 2005 Follow‐up: 3 months, 2 years Country: UK Setting: multicentre (2 sites)
Participants	Study characteristics Inclusion criteria: T2DM with microalbuminuria (UACR > 3.0 mg/mmol or 24 hours UAER > 30 mg/24 h); fluency in spoken English; < 75 years; stage of DKD: stage 3 (microalbuminuria) Exclusion criteria: none reported Baseline characteristics Number: intervention group (65); control group (59) Mean age ± SD (years): intervention group (59.2 ± 8.8); control (60.3 ± 8.6) Gender (males): intervention group (67.7%); control group (74.6%) Mean duration of diabetes ± SD (years): intervention group (10.9 ± 7.9); control group (10.7 ± 7.5) Ethnicity Caucasian/Black/Asian (%): intervention group (52.3/27.7/20.0); control group (45.8/25.4/28.8) Smoker (yes): intervention group (8); control group (13) Mean HbA1c ± SD (%): intervention group (8.2 ± 1.3); control group (8.6 ± 1.8) Co‐morbidities Not reported
Interventions	Intervention group (education + routine treatment) Education programme: University College London ‐ Diabetes Self‐management Programme Content: 2.5 hours sessions held weekly for 5 weeks plus one booster session of 2.5 hours held 3 months after the end of the intervention Weekly sessions: behavioural topics, including self‐monitoring of blood glucose, diet, exercise and medication, as well as discussion on what self‐management is and why it is important, and more general discussion of the difficulties of living with diabetes, including both practical and psychosocial difficulties Booster session: acted as a reflection on what had been learnt in previous sessions and addressed the difficulties of maintaining behaviour change over time Provider: diabetes specialist nurses and dietician Modality: face‐to‐face, a facilitator’s manual describing both the content and processes Control group (routine treatment) No additional education or attention other than to complete assessments and receive 'routine treatment' (not reported in detail) Co‐interventions or additional treatments None reported Treatment period 5 weeks
Outcomes	Reported outcomes HbA1c (%): change at 3 months Diabetes illness cognition Patient self‐management behaviours QoL Change of knowledge of DM and DKD Self‐efficacy
Notes	Additional information Trial registration: none reported A priori published protocol: none reported Conflicts of interest/disclosures: no competing interests declared Funding: "This research was supported by a health services research fellowship from the North Thames Region of the National Health Service, the UK to the first author"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: " Randomization method was by allocating participants alternately to control or intervention group" Comment: insufficient information provided about randomisation methods
Allocation concealment (selection bias)	Unclear risk	Quote: "Although alternate allocation does not ensure allocation concealment, this method was used in order to ensure a smooth flow of participants into the intervention group for organisational reasons. The analysis of baseline data demonstrated that there were no significant differences between the two groups." Comment: insufficient information provided to be sure whether the allocation of treatment groups was adequately concealed
Blinding of participants and personnel (performance bias) All objective outcomes	Low risk	Quote: "The questionnaires for both intervention and control group were completed within the diabetes clinics and administered by a research fellow. Although this individual was not involved in the delivery of the intervention, it was not possible for them to be blinded to group allocation" Comment: while this was an unblinded trial, the objective outcomes reported, such as a change in HbA1c%, were likely not influenced by whether the participants' and personnel were blinded or not
Blinding of participants and personnel (performance bias) All subjective outcomes	High risk	Quote: "The questionnaires for both intervention and control group were completed within the diabetes clinics and administered by a research fellow. Although this individual was not involved in the delivery of the intervention it was not possible for them to be blinded to group allocation" Comment: unblinded trial. The subjective self‐reported outcomes in this study could have been influenced by lack of blinding of participants and personnel
Blinding of outcome assessment (detection bias) All objective outcomes	Low risk	Quote: "The questionnaires for both intervention and control group were completed within the diabetes clinics and administered by a research fellow. Although this individual was not involved in the delivery of the intervention, it was not possible for them to be blinded to group allocation" Comment: unblinded trial. Baseline measures were by self‐report and the research fellow involved was unblinded to group allocation. Unclear if other outcomes assessors were blinded, but it's unlikely that objective outcomes would be influenced by this
Blinding of outcome assessment (detection bias) All subjective outcomes	High risk	Quote: "The questionnaires for both intervention and control group were completed within the diabetes clinics and administered by a research fellow. Although this individual was not involved in the delivery of the intervention it was not possible for them to be blinded to group allocation" Comment: unblinded trial. Baseline measures were by self‐report, and the research fellow who administered this was unblinded to group allocation. Unclear if other outcomes assessors were blinded
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote: "Attrition at follow‐up assessments was 9 per cent at immediate post‐intervention (4 participants control group, 9 participants intervention group) and 17 per cent at 3‐month follow‐up (8 participants control group, 12 participants intervention group). Individuals who did and did not complete follow‐up assessments did not differ significantly at baseline" Comment: all participants were accounted for from start to end of the trial Comment: total attrition from baseline to end of the trial was high (28%) Comment: attrition at follow‐up existed. They mention that individuals who did and did not complete follow‐up assessments did not differ significantly at baseline. For one outcome (efficacy of self‐management programme), the study reports that drop‐outs had significantly higher baseline HbA1c than programme completers. There is potential for selection bias
Selective reporting (reporting bias)	Unclear risk	Comment: all methods‐planned outcomes were reported in the results. However, no trial registration or a priori‐published protocol was provided. Some patient‐related outcomes, such as information on adverse events, the incidence of kidney death, or changes in functional measures, were not stated A priori‐published protocol: none reported
Other bias	Unclear risk	Comment: there was insufficient information to make any judgement Conflicts of Interest/Disclosures: the authors declared no competing interests Funding declared: "This research was supported by a health services research fellowship from the North Thames Region of the National Health Service, UK to the first author"

ACEi: angiotensin‐converting‐enzyme inhibitors; ACR: albumin/creatinine ratio; BP: blood pressure; CKD: chronic kidney disease; CVD: cardiovascular disease; DBP: diastolic BP; DDFQ: Dialysis Diet and Fluid Non‐Adherence Questionnaire; DESMOND: Diabetes Education and Self‐Management for Ongoing and Newly Diagnosed; DKD: diabetic kidney disease; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; ESKD: end‐stage kidney disease; HADS: Hospital Anxiety and Depression Scale; Hb: haemoglobin; HbA1c: glycolated haemoglobin; HD: haemodialysis; HDL: high‐density lipoprotein; HEIQ: Health Education Impact Questionnaire; ITT: intention‐to‐treat; KDQoL‐SF: Kidney Disease Quality of Life‐Short Form; KRT: kidney replacement therapy; LDL: low‐density lipoprotein; LVEF: left ventricular ejection fraction; MCS: mental component summary; NICE: Natioanl Institute of Clinical Excellence; NYHA: New York Heart Association; PAID: Problem Areas in Diabetes Scale; PCS: physical component summary; PD: peritoneal dialysis; QoL: quality of life; SBP: systolic BP; SCr: serum creatinine; SAS: Self‐Rating Anxiety Scale; SDSCA: Summary of Diabetes Self‐Care Activities; T1DM: type 1 DM; T2DM: type 2 DM; UACR: urinary albumin‐creatinine ratio; UAER: urinary albumin excretion ratio

Characteristics of excluded studies [ordered by study ID]

Study	Reason for exclusion
Ali 2024	Wrong population: T2DM participants with hypertension, no CKD
Bao 2021	Study retracted 2022
Binik 1993	Wrong population: non‐diabetic participants included; primary causes of ESKD were not specified
Briggs 2004	Wrong population: included participants with chronic illnesses, not just those with both DM and CKD
Calikoglu 2023	Wrong population: T2DM participants, no CKD
CAPTION 2010	Wrong population: hypertensive participants with CKD or DM, not necessarily both
Cortes‐Sanabria 2008	Wrong population: non‐co‐existing DM and CKD participants included, no separate data for those with DKD available
DePatis 2019	Wrong population: not all participants met CKD requirements
Devins 2003	Wrong population: non‐diabetic participants included; primary causes of CKD were not specified
Didjurgeit 2002	Wrong population: included non‐CKD participants and those with other diabetic complications (e.g. diabetic retinopathy) instead of DKD; no separate data for those with DKD available
DNETT‐Japan 2010	Wrong intervention: usual care versus multifactorial intervention (which includes treatment and pharmacological treatments); outcome measures do not report according to the effect of the educational intervention
Dong 2019	Wrong intervention: both groups undertook educational programmes as part of their therapy
Du 2022a	Wrong population: included overweight participants with and without CKD and diabetes
Ford 2004	Wrong population: non‐diabetic participants included; primary causes of ESKD were not specified
FROM‐J 2010	Wrong population: not all participants had DM
GP‐Prompt 2018	Wrong population: health care professional training
Hall 2004	Wrong population: non‐diabetic participants included; primary causes of ESKD were not specified
Helou 2016	Wrong intervention: usual care versus multidisciplinary interventions in a cross‐over design
HHK 2018	Wrong intervention: four groups all receiving usual care + a different additional type of multidisciplinary treatment
Hoto 2010	Wrong intervention: more than just education (e.g. transport arrangement to local pharmacy if required)
Kawabata 2022	Wrong population: non‐co‐existing DM and CKD participants included; no separate data for those with DKD available
Kawai 2021	Wrong intervention: electronic prompting via a smart‐phone
Korniewicz 1994	Wrong population: non‐diabetic participants included; primary causes of ESKD were not specified
Kuningas 2020	Wrong population: non‐diabetic kidney transplant recipients
Leon 2006	Wrong intervention: confounding with drug therapy (e.g. educational programme+other drugs+routine treatment versus routine treatment); primary causes of ESKD were not specified
Leung 2005	Wrong intervention: compared a healthcare protocol for healthcare professionals
Lim 2021a	Wrong population: non‐CKD participants included
Litvin 2020	Wrong population: healthcare professional training
Manns 2005	Wrong population: non‐diabetic participants included; primary causes of ESKD were not specified
MDRD Study 1 1989	Wrong population: non‐co‐existing DM and CKD participants included; no separate data for those with DKD available; primary causes of CKD were not specified
Naimark 2001	Wrong population: healthcare professional screening
NCT05319600	Wrong intervention: technology‐delivered activity programme
NCT05357742	Wrong intervention: both groups received a manualised study intervention for DKD
NCT06325917	Wrong population: T2DM participants; CKD participants excluded
NCT06444074	Wrong population: T2DM participants; CKD participants excluded
Nelson 2018	Wrong population: non‐co‐existing DM and CKD participants included
Nozaki 2005	Wrong population: non‐co‐existing DM and CKD participants included; primary causes of ESKD were not specified
Osaki 2017	Wrong intervention: both groups undertook educational programmes as part of their therapy
Othman 2022	Wrong population: post‐transplant diabetes
Othman 2024	Wrong population: post‐transplant diabetes
PANDIA‐IRIS 2021	Wrong intervention: electronic monitoring of medication adherence
QICKD 2009	Wrong intervention: compared a healthcare protocol for healthcare professionals
Rachmani 2005	Wrong population: DM participants, no CKD
REDEEM 2013	Wrong population: DM participants, no CKD
Roddy 2022	Wrong population: non‐CKD participants included
Shi 2020	Wrong population: non‐CKD participants included
STENO‐2 1999	Wrong intervention: usual care versus multifactorial intervention (which includes treatment and pharmacological treatments); outcome measures do not report according to the effect of the educational intervention
STOP‐DKD 2018	Wrong intervention: usual care versus multifactorial intervention (which includes treatment and pharmacological treatments); outcome measures do not report according to the effect of the educational intervention
SURE 2009	Wrong intervention: usual care versus multifactorial intervention (which includes treatment and pharmacological treatments); outcome measures do not report according to the effect of the educational intervention
Tan 2019	Wrong population: non‐CKD participants included
Tsay 2003	Wrong population: non‐co‐existing DM and CKD participants included; primary causes of ESKD were not specified
Tsay 2004c	Wrong population: non‐co‐existing DM and CKD participants included; primary causes of ESKD were not specified
Tsay 2005	Wrong population: non‐co‐existing DM and CKD participants included; primary causes of ESKD were not specified
Tsuji‐Hayashi 2000	Wrong population: non‐co‐existing DM and CKD participants included; primary causes of ESKD were not specified
Tuot 2018	Wrong population: healthcare professional training
Ueki 2021	Wrong population: non‐CKD participants included
Woolf 2017	Wrong population: non‐co‐existing DM and CKD participants included
Yalcin 2008	Wrong population: T2DM participants, no CKD
Zhu 2021	Wrong population: T2DM participants, no CKD

CKD: chronic kidney disease; DKD: diabetic kidney disease; DM: diabetes mellitus; ESKD: end‐stage kidney disease; HD: haemodialysis; PD: peritoneal dialysis; T2DM: type 2 DM

Characteristics of studies awaiting classification [ordered by study ID]

NCT00782847.

Methods	Study design Parallel RCT Endpoint classification: efficacy study Masking: open‐label Primary purpose: supportive care Setting: single centre Country: Germany
Participants	Study characteristics Inclusion criteria: 18 to 80 years; DM; proven DKD by histological/lab findings and/or discretion of nephrologist; ability to understand the German language Exclusion criteria: ESKD and/or dialysis; unable or unwilling to follow the protocol; pregnant women; discretion of nephrologist Enrolment: 125
Interventions	Intervention group (behavioural) DiaNe consultation and support programme The DiaNe consultation and support programme for clients with diabetic nephropathy consists of 4, 90 to 120‐minute sessions conducted every week for 4 weeks Control group No intervention Received standard care by a diabetologist and/or nephrologist
Outcomes	Planned outcomes Deterioration of kidney function in DKD Time frame: 13 months Designated safety issue: no HbA1c Time frame: 13 months Designated safety issue: no
Notes	Study completed January 2007; no data posted Sponsor: DiaNe HCM GmbH

Suvamat 2023.

Methods	Study design Cluster RCT Study duration: unclear Follow‐up: 14 weeks Setting: multicentre (6 districts) Country: Thailand
Participants	Study characteristics Inclusion criteria: aged 40 to 70 years with diabetes, with or without hypertension, and CKD stage 3 (GFR 30 to 59 mL/min/1.73 m2); BP > 140/90 mm Hg at least once in previous 6 months; HbA1c > 7%; communicate, read and write in Thai, live with their family, no complications or severe illnesses during study Exclusion criteria: not reported Baseline characteristics Number: intervention group (38); control group (38) Mean age ± SD (years): intervention group (65.5 ± 5.44); control group (65.23 ± 4.41) Gender (M/F): intervention group (9/29); control group (12/26)
Interventions	Intervention group Face‐to‐face group activities with motivational interviews Control group Usual care
Outcomes	Reported outcomes BMI HbA1c BP eGFR Creatinine Albuminuria
Notes	Additional information Funding: "The study was supported by Praboromarajchanok Institute, Thailand."

BMI: body mass index; BP: blood pressure; CKD: chronic kidney disease; DKD: diabetic kidney disease; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; ESKD: end‐stage kidney disease; HbA1c: glycolated haemoglobin; RCT: randomised controlled trial

Characteristics of ongoing studies [ordered by study ID]

NCT03413215.

Study name	Effects of multidisciplinary intensive targeted care in improving diabetes outcomes: a pilot study in Singapore (IDEALS)
Methods	Study design Pilot parallel RCT Open‐label study Purpose: prevention Country: Singapore Setting: single centre
Participants	Study characteristics Inclusion criteria: T2DM aged 21 to 70 years; poorly controlled diabetes with microalbuminuria as defined by the following HbA1C > 9.0% with eGFR 30 to 60 mL/min and/or proteinuria > 0.5 g/day and/or urine microalbumin‐creatinine ratio > 300 mg/g on 2 consecutive measurements 3 months apart Exclusion criteria: T1DM (a history of ketosis at diagnosis or continuous requirement of insulin within one year of diagnosis); psychiatric conditions on medication; on weight loss medications or have had bariatric surgery; life expectancy less than 12 months due to advanced cancers or other life‐threatening conditions Planned enrolment: 50
Interventions	Intervention group The intensive group will receive additional counselling and education by the diabetes nurse educator and medical social worker on self‐care and coping strategies for diabetes and see the renal pharmacist for more intensive titration of antihypertensive medication between doctor visits. They will also be loaned blood pressure monitors and glucometers with test strips to perform self‐monitoring at home in between outpatient visits. Smartphone and online technologies will be utilized to improve remote monitoring, education and self‐care Provided with a BP machine, glucometer and test strips, and instructed how to use either a written or smartphone logbook, photograph their meals and use smartphone apps to measure daily activity. Diabetes nurse educators will contact patients in between visits to reinforce adherence and self‐monitoring. Medical social workers will conduct at least 6 face‐to‐face sessions, at 3 weeks, then less frequently, on essential self‐care behaviours in people with diabetes: healthy eating, being physically active, monitoring of blood sugar, compliance with medications, problem‐solving, healthy coping skills, and risk‐reduction behaviour. Renal pharmacists will see patients at 2‐4 week intervals for 3 months after the first clinic visit and subsequently every 3‐6 months. They will review the patient's compliance, laboratory results and home BP, educate the patient and titrate antihypertensives to meet the BP goal. Physician referrals will be made for severe hypertension or hypotension, or intolerable side effects. Control group Standard care: consists of 4‐monthly clinic visits for review of BP, HbA1c and other investigations, titration of medications, counselling with the diabetes nurse educator, and provision of educational materials on diabetes.
Outcomes	Planned outcomes Composite of Incidence of all diabetes‐related endpoints Cardiovascular events (acute myocardial infarction, revascularisation procedures, heart failure, unstable angina, arrhythmia, stroke, transient ischaemic attacks requiring hospital admission) and related death CKD (eGFR < 60 mL/min/1.73 m2) or ESKD (dialysis and/or eGFR < 15 mL/min/1.73 m2) and related death Visual impairment (corrected visual acuity of 20/200 or worse) or eye surgery (cataract removal, retinal surgery and vitrectomy) Lower extremity amputation or foot ulcers requiring hospitalisation Major infections ‐ pulmonary and non‐pulmonary requiring hospitalisations All‐site cancers Death Proportions of patients with improved control of risk factors defined as: a) 2 or more of the 'ABC' targets: i) HbA1c < 7% ii) BP < 130/80 mm Hg iii) LDL‐cholesterol < 2.6 mmol/L b) and/or c) 2 of the following changes in risk factor control: i) at least 0.5% reduction in HbA1c ii) at least 5 mm Hg reduction in SBP iii) at least 0.5 mmol/L reduction in LDL‐cholesterol iv) at least 3% reduction in body weight
Starting date	Actual: 1 March 2019 Estimated completion date: 31 December 2022
Contact information	Contact: Ann Cheung +6568502691; ann.cheung.n.s@singhealth.com.sg Contact: Nur Shameerah Abdul Halim +6568501902; nur_shameerah@cgh.com.sg
Notes	Current status: unknown

BP: blood pressure; CKD: chronic kidney disease; DM: diabetes mellitus; eGFR: estimated glomerular filtration rate; ESKD: end‐stage kidney disease; HbA1c: glycolated haemoglobin; LDL: low‐density lipoprotein; RCT: randomised controlled trial; SBP: systolic BP; T1DM: type 1 DM; T2DM: type 2 DM

Differences between protocol and review

The risk of bias assessment tool has been used in place of the quality assessment checklist in accordance with the new Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2022).

Contributions of authors

• Brydee Johnston: selection of studies, assessment of studies, data extraction, data analysis, writing and revising of protocol and full text review

• Tess Cooper: selection of studies, assessment of studies, resolution of disagreements, data extraction, revising of protocol

• David Tunnicliffe: revising of full text review, resolution of disagreements, expertise, suggestions and corrections

• Nicole M Evangelidis: selection of studies, assessment of studies

• Suetonia C Palmer: expertise, suggestions and corrections

• Pamela Lopez‐Vargas: suggestions and corrections

Sources of support

Internal sources

• Cochrane Kidney and Transplant, Australia

  This review was updated for Cochrane Kidney and Transplant Evidence Review Team for the KDIGO 2020 Clinical Practice Guidelines for Diabetes Management in Chronic Kidney Disease.

External sources

• No sources of support provided

Declarations of interest

• Brydee Cashmore: No relevant interests were disclosed

• Tess E Cooper: No relevant interests were disclosed

• Nicole M Evangelidis: No relevant interests were disclosed

• Suetonia C Palmer: No relevant interests were disclosed

• Pamela Lopez‐Vargas: No relevant interests were disclosed

• David J Tunnicliffe: No relevant interests were disclosed

New search for studies and content updated (conclusions changed)