Low energy diet plus supervised exercise vs. usual care alone in people with early-onset type 2 diabetes (RESET for Remission): a randomised, open-label, blinded-endpoint efficacy trial

Background Low energy diets (LED) can induce type 2 diabetes remission but have not been studied in combination with structured supervised exercise. We aimed to determine if a combined intervention could induce remission in early-onset type 2 diabetes (EOT2D ≤ 45 years of age), a population with high lifetime risk of complications. Methods Across 3 centres in England and Canada, we conducted a randomised, open-label, blinded endpoint efficacy trial among adults 18–45 years of age with EOT2D and obesity, not on insulin therapy. The groups were usual care alone vs. an intervention combining 800–900 kcal/day LED, twice-weekly supervised (aerobic, resistance) and once-weekly independent exercise (weeks 1–12), followed by a weight-maintenance diet with independent exercise (weeks 13–24). An independent statistician generated web-based randomisation sequences (1:1, country- and sex-stratified, variable block size). The primary outcome was remission at 24 weeks (Hb A1c < 6.5% [48 mmol/mol], without glucose-lowering medication ≥12 weeks). The primary efficacy and harms analysis was in all randomised individuals, assuming no remission when data were unavailable. Secondary endpoints included cardiorespiratory fitness, body composition, and cardiac structure. The trial is registered at ISRCTN (15487120) and is now closed. Findings We randomised 96 participants (mean age 38 years, BMI 35.2 kg/m 2 ) between September 24, 2021 and June 6, 2025 (intervention group: 24 female, 26 male with 18 European, 17 South Asian, 15 Other ethnicity; control group: 21 female, 25 male with 19 European, 10 South Asian, 17 Other ethnicity). In total, 86 (90%) attended final assessments. Remission at 24 weeks occurred in 27/50 (54%) of intervention participants vs. 2/46 (4%) control participants (50% difference, 95% CI 33%–64%; adjOR 21.6, 95% CI 6.2 to 114.5), without serious adverse events. Most intervention group participants experienced at least one adverse event (43/50 vs. 6/46), mainly early LED effects (e.g., constipation, headache, dizziness, fatigue) that resolved. Interpretation High remission rates signal feasibility and efficacy of a combined LED and intensive exercise intervention in EOT2D, justifying examination of synergistic benefits beyond remission. Funding United Kingdom Medical Research Council, Canadian Institutes of Health Research, John R. McConnell Foundation.