Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial

Lean, M. E.J. et al. (2019) Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes and Endocrinology, 7(5), pp. 344-355. (doi: 10.1016/S2213-8587(19)30068-3) (PMID:30852132)

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Background: The DiRECT trial assessed remission of type 2 diabetes during a primary care-led weight-management programme. At 1 year, 68 (46%) of 149 intervention participants were in remission and 36 (24%) had achieved at least 15 kg weight loss. The aim of this 2-year analysis is to assess the durability of the intervention effect. Methods: DiRECT is an open-label, cluster-randomised, controlled trial done at primary care practices in the UK. Practices were randomly assigned (1:1) via a computer-generated list to provide an integrated structured weight-management programme (intervention) or best-practice care in accordance with guidelines (control), with stratification for study site (Tyneside or Scotland) and practice list size (>5700 or ≤5700 people). Allocation was concealed from the study statisticians; participants, carers, and study research assistants were aware of allocation. We recruited individuals aged 20–65 years, with less than 6 years' duration of type 2 diabetes, BMI 27–45 kg/m2, and not receiving insulin between July 25, 2014, and Aug 5, 2016. The intervention consisted of withdrawal of antidiabetes and antihypertensive drugs, total diet replacement (825–853 kcal per day formula diet for 12–20 weeks), stepped food reintroduction (2–8 weeks), and then structured support for weight-loss maintenance. The coprimary outcomes, analysed hierarchically in the intention-to-treat population at 24 months, were weight loss of at least 15 kg, and remission of diabetes, defined as HbA1c less than 6·5% (48 mmol/mol) after withdrawal of antidiabetes drugs at baseline (remission was determined independently at 12 and 24 months). The trial is registered with the ISRCTN registry, number 03267836, and follow-up is ongoing. Findings: The intention-to-treat population consisted of 149 participants per group. At 24 months, 17 (11%) intervention participants and three (2%) control participants had weight loss of at least 15 kg (adjusted odds ratio [aOR] 7·49, 95% CI 2·05 to 27·32; p=0·0023) and 53 (36%) intervention participants and five (3%) control participants had remission of diabetes (aOR 25·82, 8·25 to 80·84; p<0·0001). The adjusted mean difference between the control and intervention groups in change in bodyweight was −5·4 kg (95% CI −6·9 to −4·0; p<0·0001) and in HbA1c was −4·8 mmol/mol (–8·3 to −1·4 [–0·44% (–0·76 to −0·13)]; p=0·0063), despite only 51 (40%) of 129 patients in the intervention group using anti-diabetes medication compared with 120 (84%) of 143 in the control group. In a post-hoc analysis of the whole study population, of those participants who maintained at least 10 kg weight loss (45 of 272 with data), 29 (64%) achieved remission; 36 (24%) of 149 participants in the intervention group maintained at least 10 kg weight loss. Serious adverse events were similar to those reported at 12 months, but were fewer in the intervention group than in the control group in the second year of the study (nine vs 22). Interpretation: The DiRECT programme sustained remissions at 24 months for more than a third of people with type 2 diabetes. Sustained remission was linked to the extent of sustained weight loss.

Item Type:Articles
Additional Information:This study was funded by Diabetes UK as a Strategic Research Initiative (award number 13/0004691)
Glasgow Author(s) Enlighten ID:McConnachie, Professor Alex and Brosnahan, Dr Naomi and Welsh, Professor Paul and Kean, Ms Sharon and McIlvenna, Ms Yvonne and Thom, Dr George and Ford, Professor Ian and Messow, Dr Martina and Lean, Professor Michael and Sattar, Professor Naveed and Leslie, Dr Wilma
Authors: Lean, M. E.J., Leslie, W. S., Barnes, A. C., Brosnahan, N., Thom, G., McCombie, L., Peters, C., Zhyzhneuskaya, S., Al-Mrabeh, A., Hollingsworth, K., Rodrigues, A. M., Rehackova, L., Adamson, A. J., Sniehotta, F. F., Mathers, J. C., Ross, H. M., McIlvenna, Y., Welsh, P., Kean, S., Ford, I., McConnachie, A., Messow, C.-M., Sattar, N., and Taylor, R.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > General Practice and Primary Care
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Lancet Diabetes and Endocrinology
ISSN (Online):2213-8595
Published Online:06 March 2019
Copyright Holders:Copyright © 2019 Elsevier
First Published:First published in Lancet Diabetes and Endocrinology 7(5): 344-355
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
614614Reversal of T2DM to normal glucose tolerance using non-surgical weight management with low-energy liquid- diet and long-term maintenance, within routine NHS care: study extensionMichael LeanDiabetes UK (DIABETUK)13/0004691MVLS MED -HUMAN NUTRITION