Elsevier

The Lancet

Volume 391, Issue 10120, 10–16 February 2018, Pages 541-551
The Lancet

Articles
Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial

https://doi.org/10.1016/S0140-6736(17)33102-1Get rights and content

Summary

Background

Type 2 diabetes is a chronic disorder that requires lifelong treatment. We aimed to assess whether intensive weight management within routine primary care would achieve remission of type 2 diabetes.

Methods

We did this open-label, cluster-randomised trial (DiRECT) at 49 primary care practices in Scotland and the Tyneside region of England. Practices were randomly assigned (1:1), via a computer-generated list, to provide either a weight management programme (intervention) or best-practice care by guidelines (control), with stratification for study site (Tyneside or Scotland) and practice list size (>5700 or ≤5700). Participants, carers, and research assistants who collected outcome data were aware of group allocation; however, allocation was concealed from the study statistician. We recruited individuals aged 20–65 years who had been diagnosed with type 2 diabetes within the past 6 years, had a body-mass index of 27–45 kg/m2, and were not receiving insulin. The intervention comprised withdrawal of antidiabetic and antihypertensive drugs, total diet replacement (825–853 kcal/day formula diet for 3–5 months), stepped food reintroduction (2–8 weeks), and structured support for long-term weight loss maintenance. Co-primary outcomes were weight loss of 15 kg or more, and remission of diabetes, defined as glycated haemoglobin (HbA1c) of less than 6·5% (<48 mmol/mol) after at least 2 months off all antidiabetic medications, from baseline to 12 months. These outcomes were analysed hierarchically. This trial is registered with the ISRCTN registry, number 03267836.

Findings

Between July 25, 2014, and Aug 5, 2017, we recruited 306 individuals from 49 intervention (n=23) and control (n=26) general practices; 149 participants per group comprised the intention-to-treat population. At 12 months, we recorded weight loss of 15 kg or more in 36 (24%) participants in the intervention group and no participants in the control group (p<0·0001). Diabetes remission was achieved in 68 (46%) participants in the intervention group and six (4%) participants in the control group (odds ratio 19·7, 95% CI 7·8–49·8; p<0·0001). Remission varied with weight loss in the whole study population, with achievement in none of 76 participants who gained weight, six (7%) of 89 participants who maintained 0–5 kg weight loss, 19 (34%) of 56 participants with 5–10 kg loss, 16 (57%) of 28 participants with 10–15 kg loss, and 31 (86%) of 36 participants who lost 15 kg or more. Mean bodyweight fell by 10·0 kg (SD 8·0) in the intervention group and 1·0 kg (3·7) in the control group (adjusted difference −8·8 kg, 95% CI −10·3 to −7·3; p<0·0001). Quality of life, as measured by the EuroQol 5 Dimensions visual analogue scale, improved by 7·2 points (SD 21·3) in the intervention group, and decreased by 2·9 points (15·5) in the control group (adjusted difference 6·4 points, 95% CI 2·5–10·3; p=0·0012). Nine serious adverse events were reported by seven (4%) of 157 participants in the intervention group and two were reported by two (1%) participants in the control group. Two serious adverse events (biliary colic and abdominal pain), occurring in the same participant, were deemed potentially related to the intervention. No serious adverse events led to withdrawal from the study.

Interpretation

Our findings show that, at 12 months, almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs. Remission of type 2 diabetes is a practical target for primary care.

Funding

Diabetes UK.

Introduction

Type 2 diabetes affects almost one in ten adults in the UK, and 422 million adults worldwide.1, 2 Most people with type 2 diabetes have disease-related morbidity and reduced longevity. The disease is particularly devastating for the growing numbers of younger people affected, who tend to be more obese and lose more life-years through diabetes.3 Current guidelines for management of type 2 diabetes focus heavily on multiple drug treatments to reduce blood glucose and the associated elevated risks of cardiovascular disease, but life expectancy remains substantially reduced.

Type 2 diabetes is strongly related to weight gain in adult life and accumulation of excess fat within the liver and pancreas. The twin cycle hypothesis,4 which postulated that type 2 diabetes is caused specifically by excess fat within the liver and pancreas, was tested by inducing negative energy balance with a 600–700 kcal/day diet. Liver insulin resistance and fat content normalised within 7 days, with first-phase insulin response and pancreas fat content normalising over 8 weeks.5 In a subsequent parallel-group study,6 the underlying changes were shown to remain stable over a 6 month period of isocaloric eating. These pathophysiological studies established how and why people with type 2 diabetes can be returned to normal glucose control by calorie restriction. The challenge remained to test whether such an intervention was practicable in routine primary care. Other studies involving weight loss of at least 10–15 kg have been shown to achieve normalisations of blood glucose in people with short-duration type 2 diabetes,7, 8, 9, 10 but no previous trial based on dietary change has assessed sustained (ie, ≥1 year) disease remission as a primary outcome.

Research in context

Evidence before this study

Between Jan 1, 1980, and Oct 30, 2017, we searched clinical guidelines and published reports for non-surgical clinical trials with a primary outcome of remission of type 2 diabetes. Our search terms were “diabetes and remission” and “clinical trial”, and we restricted the search to English-language publications only. No trials were identified. Evidence-based clinical guidelines for type 2 diabetes focus on pharmacological treatments to reduce blood glucose and glycated haemoglobin (HbA1c). Diet and lifestyle are mentioned as part of efforts to control glycaemia levels, but diabetes remission by this route is rarely discussed. Weight gain, however, is a dominant causal factor behind type 2 diabetes in susceptible individuals. Although bariatric surgery can achieve remission of diabetes in about 75% of people with type 2 diabetes, only a small proportion could or would wish to undergo surgical treatments.

Added value of this study

Our DiRECT study provides the first evidence from a randomised trial of a dietary and lifestyle intervention with remission of type 2 diabetes as a primary outcome. The findings show that more than a quarter of people with type 2 diabetes of up to 6 years' duration are interested in using a practical weight management programme delivered by existing staff in primary care (including a high proportion of men), and that almost half of those undertaking the intervention can achieve and maintain remission at 12 months. Achieved weight reductions were around 10 kg on average in the intervention group.

Implications of all the available evidence

DiRECT is a pragmatic trial done under real-life, primary care conditions in a sample of people with type 2 diabetes typical of those managed routinely in this setting. Relatively low-intensity training and support of existing staff, and appropriate resource redistribution, could facilitate provision of this intervention and dissemination of the results widely across health services. This approach would offer the chance to achieve remission of type 2 diabetes and its associated benefits, including improved quality of life. The potential personal and health-service-related benefits are considerable.

We did the Diabetes Remission Clinical Trial (DiRECT) to assess whether effective weight management, delivered in the primary care setting, could produce sustained remission of type 2 diabetes.

Section snippets

Study design and participants

We did this open-label, cluster-randomised trial at 49 primary care practices in Scotland and the Tyneside region of England. General practices (GPs) representing populations with a wide range of social and geographic features were invited to participate by the Primary Care Research Network (PCRN) in Scotland, and North East Commissioning Support in Tyneside. Ethics approval was granted by West 3 Ethics Committee in January, 2014, with approvals by the National Health Service (NHS) health board

Results

Recruitment and baseline data have been published elsewhere.17 Between July 25, 2014, and Aug 5, 2016, we recruited 306 individuals from 49 intervention (n=23) and control (n=26) practices; 149 participants per group comprised the intention-to-treat population (figure 1). Baseline characteristics were similar between groups (table 1).17

23 (8%) participants were lost to follow-up at 12 months, with 128 (86%) participants in the intervention group and 147 (99%) participants in the control group

Discussion

Our findings confirm that type 2 diabetes of up to 6 years' duration is not necessarily a permanent, lifelong condition. Weight loss sufficient to achieve remission can be attained in many individuals by use of an evidence-based structured weight management programme delivered in a non-specialist community setting by routine primary care staff. Just less than a quarter of participants in the intervention group achieved weight loss of 15 kg or more at 12 months, half maintained more than 10 kg

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