AIM:To identify predictors of type 2 diabetes remission in the intervention arm of DiRECT (Diabetes Remission Clinical Trial).METHODS:Participants were aged 20-65 years, with type 2 diabetes duration of <6 years and BMI 27-45 kg/m2 , and were not receiving insulin. Weight loss was initiated by total diet replacement (825-853 kcal/day, 3-5 months, shakes/soups), and weight loss maintenance support was provided for 2 years. Remissions (HbA1c <48 mmol/mol [<6.5%], without antidiabetes medications) in the intervention group (n = 149, mean age 53 years, BMI 35 kg/m2 ) were achieved by 68/149 participants (46%) at 12 months and by 53/149 participants (36%) at 24 months. Potential predictors were examined by logistic regression analyses, with adjustments for weight loss and effects independent of weight loss.RESULTS:Baseline predictors of remission at 12 and 24 months included being prescribed fewer antidiabetes medications, having lower triglyceride and gamma-glutamyl transferase levels, and reporting better quality of life with less anxiety/depression. Lower baseline HbA1c was a predictor at 12 months, and older age and male sex were predictors at 24 months. Being prescribed antidepressants predicted non-remission. Some, but not all effects were explained by weight loss. Weight loss was the strongest predictor of remission at 12 months (adjusted odds ratio per kg weight loss 1.24, 95% CI 1.14, 1.34; P < 0.0001) and 24 months (adjusted odds ratio 1.23, 95% CI 1.13, 1.35; P <0.0001). Weight loss in kilograms and percentage weight loss were equally good predictors. Early weight loss and higher programme attendance predicted more remissions. Baseline BMI, fasting insulin, fasting C-peptide and diabetes duration did not predict remission.CONCLUSIONS:Other than weight loss, most predictors were modest, and not sufficient to identify subgroups for which remission was not a worthwhile target.

Background: DiRECT reported diabetes remission at one year for 46% of participants allocated to an integrated structured weight management programme. We now assess two-year findings. Methods: DiRECT is an open-label, cluster-randomised, controlled trial in primary care practices randomised to a weight management programme (intervention) or best-practice care by guidelines (control). We recruited individuals aged 20–65 years, with <6 years duration of type 2 diabetes, body-mass index 27–45 kg/m, and not receiving insulin. The intervention comprised withdrawal of anti-diabetes and antihypertensive drugs, total diet replacement (825–853 kcal/day formula diet) for 12-20 weeks, stepped food reintroduction (2–8 weeks), and then structured support for weight loss maintenance. Co-primary outcomes, analysed hierarchically, were weight loss >15 kg, and remission of diabetes, defined as HbA1c <6·5% (<48 mmol/mol) with no anti-diabetes medications. Findings: At 24 months, 53/149 (35·6%) of those commencing the intervention and 5/149 (3·4%) in the control group (adjusted odds ratio 25·8, 95% CI 8·3,80·8; p<0·0001) had remission, and 11·4% of intervention and 2·0% of the control group (adjusted odds ratio 8·2 (2·2,30·0), p=0·0015) had weight loss ≥15kg. Of those maintaining ≥10kg weight loss (45/272), 64% (29/45) achieved remission, and 24.2% (36/149) of the intervention group maintained ≥10kg weight loss. Adjusted mean differences between groups were, in changes in body weight -5·4 kg, (-6·9,-4·0), p<0·0001, in HbA1c -4·8 mmol/mol, (-8·3,-1·4), p=0·0063 despite >50% fewer anti-diabetes agent use in intervention group, and SBP -3·4 mmHg, (-6·7,-0·2), p=0·0397. Serious adverse events were similar at 12 months, but fewer occurred in intervention than control in the second year (9 vs. 22). Quality of life improved more from baseline in the intervention than the control group, adjusted mean difference 4·6 (0·4,8·9, p=0·032). Interpretation: This programme sustained remissions at 24 months for over a third of people with type 2 diabetes. Weight loss of ≥10 kg provides remission for two thirds. Funding: Diabetes UK.

Aims:To provide a qualitative evaluation of a 12-week TDR stage of the DiRECT intervention delivered in UK primary care,aiming to reverse Type 2 diabetes. Methods:Participants matched for gender and socioeconomic status across trial sites were interviewed at baseline (T1), six weeks into the TDR (T2) and two weeks after food reintroduction (FR)(T3). The interviews were semi-structured, audio-recorded, transcribed verbatim and analysed using the framework approach. Results: Out of 34 intervention participants interviewed at T1, 27 were available for a follow-up at T2 and 25 were available at T3. Eight participants withdrew from the study during the TDR. Narratives of 21 participants with complete data were analysed. Desiring normality in the form of normal blood glucose levels,body mass index or the ability to wear normal clothes and eat normal food were the main drivers to taking part in the study. The TDR phase was perceived as challenging but somewhat easier than anticipated. Willpower, use of behaviour–regulation strategies,social roles, behavioural independence and social and clinical support were vital determinants of adherence. Both the TDR and FR stages required resolving cognitive and emotional goal conflicts. Transition to regular food was perceived as destabilising and required increased effort, re-designing of one’s ‘Foodrobe’ and continuous support. Summary: Experience with the weight loss stage of the DiRECT intervention for diabetes remission was positive for most participants, but clinical and social support proved essential for a successful completion.