The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial

Wilma S. Leslie, Ian Ford, Naveed Sattar, Kieren G. Hollingsworth, Ashley Adamson, Falko F. Sniehotta, Louise McCombie, Naomi Brosnahan, Hazel Ross, John C. Mathers, Carl Peters, George Thom, Alison Barnes, Sharon Kean, Yvonne McIlvenna, Angela Rodrigues, Lucia Rehackova, Sviatlana Zhyzhneuskaya, Roy Taylor, Mike E. J. Lean

Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces >15 kg weight loss in 33 % of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion. The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response. Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m(2). Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction ≥ 15 kg and HbA1c <48 mmol/mol at one year. Further follow-up at 2 years. This study will establish whether a structured weight management programme, delivered in Primary Care by practice nurses or dietitians, is a viable treatment to achieve T2DM remission. Results, available from 2018 onwards, will inform future service strategy. Current Controlled Trials ISRCTN03267836 . Date of Registration 20/12/2013.