New research to be presented at the Annual Meeting of The European Association for the Study of Diabetes (EASD) in Milan, Italy (Sept 28 – Oct 2) and published in The Lancet Regional Health Americas journal shows that in people who have developed early onset type 2 diabetes (EOT2D) (aged under 45 years), around half these T2D cases can be reversed with a low-energy diet combined with a structured exercise programme. The study is by Professor Kaberi Dasgupta, McGill Director of the Division of General Internal Medicine, McGill University, Montreal, QC, Canada, and Professor Thomas Yates, University of Leicester, UK, and colleagues.
Early-onset type 2 diabetes (EOT2D) is a distinct and growing clinical phenotype with rapid deterioration in blood sugar control, early onset of complications, and lower life expectancy than later onset T2D. Low energy diets (LEDs) can reduce glucose levels below T2D diagnostic thresholds without medication (T2D remission). Adding structured exercise may provide synergistic benefits including greater fitness, muscle mass preservation, enhanced cardiac function, and lower insulin resistance. The researchers evaluated the efficacy of combining a LED with supervised exercise on remission at 24 weeks in EOT2D, a condition meriting a potent intervention to arrest its rapid evolution, comparing it to usual care.
Across 3 centres in England and Canada (affiliated with the University of Leicester, UK, McGill University (Montreal), and the University of Alberta, Edmonton), conducted a randomised, open-label, blinded endpoint efficacy trial among adults 18 to 45 years of age with EOT2D and obesity, not on insulin therapy. The groups were usual care alone versus 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). The primary outcome was remission at 24 weeks (assessed by glycated haemobglobin (HbA1c < 6·5% [48 mmol/mol]), and being without glucose-lowering medication for at least 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.
Participants stopped all glucose- and blood pressure-lowering medication (in the absence of albuminuria) with initiation of the 800-900 kcal/day diet (30% protein, 50% carbohydrate, 20% fat). They were encouraged to consume at least 2 litres of calorie-free fluid daily and provided a fibre-based laxative for use as required. The first two weeks comprised total meal replacement (Optifast). Weeks 3 to 12 continued the same caloric intake with more variety (Optifast in UK and ProtiDiet in Canada), allowing one food-based meal per day (60 to 90 g protein from all sources combined, one portion of fruit, two portions of non-starchy vegetables).
The study randomised 96 participants (40 UK, 56 Canada) between September 24, 2021 and June 6, 2025 (24 female, 26 male intervention group; 21 female, 25 male control group; mean age 38 years, BMI 35·2 kg/m2) among whom 86 (90%) attended final assessments. Remission at 24 weeks occurred in 27/50 (54%) of intervention participants versus 2/46 (4%) control participants – with statistical analysis showing after adjustment that those in the intervention group were 21 times more likely to achieve remission than those in the control group.
The 47 participants in the intervention group had a mean weight of 100.7kg at baseline, while the 43 participants in the control group had a mean weight of 103.2kg. Weight loss between weeks 0 and 24 in the intervention group was 8.4 kg, leaving intervention participants with an average weight of 92.3kg, while weight loss between weeks 0 and 24 in the control group was 1.2 kg, leaving control participants with a mean weight of 102.0 kg. Statistical adjustment showed on average intervention participants lost 7.5 kg more than control participants by week 24, which included 6.6 more kg of fat mass lost.
Remission was achieved without severe adverse events. Most intervention group participants experienced at least one adverse event (43/50 vs. 6/46), mainly early low energy diet effects (e.g., constipation, headache, dizziness, fatigue) that resolved.
The authors say: "Our findings demonstrate the feasibility and efficacy of combining structured aerobic and resistance exercise with a low energy diet in early onset type 2 diabetes, supporting its potential to deliver substantial and holistic health and well-being benefits alongside diabetes remission.
"Our remission rates are at the upper end of those previously reported in the literature for trials of similar duration, reinforcing the potential of structured lifestyle interventions to support clinically meaningful remission, while demonstrating for the first time that such effects can be achieved in a multi-ethnic population with early onset type 2 diabetes through a combined low energy diet and structured exercise intervention."
They highlight that all weight loss programmes, including low energy diets for type 2 diabetes remission, are followed by a period of either partial or full weight regain for most people. Weight loss driven by lower energy intake alone is associated with reductions in both fat and fat-free mass, and there is some evidence that weight regain may preferentially restore fat over fat-free mass, resulting in a net loss of fat-free mass and an increased risk of sarcopenia over time. They say: "Our RESET for Remission study targeted muscle during the intensive weight loss phase through resistance training, and our findings indicate fat-free mass and muscle preservation is achievable with rapid weight loss. Preserving muscle during remission-oriented weight loss may have important implications for long-term metabolic health, physical function, and disease trajectory. This requires examination in a longer-term study."
They conclude: "By focusing specifically on early onset type 2 diabetes, our trial addresses a growing clinical population, characterised by elevated cardiovascular disease risk, greater cumulative complication burden, and poor long-term outcomes…In summary, RESET for Remission demonstrated that in early onset type 2 diabetes, combining structured aerobic and resistance exercise with a low-calorie diet produces high remission rates, induces fat loss while preserving muscle mass, improves muscle quality and function, enhances cardiovascular health, and leads to meaningful improvements in patient-reported outcomes. As the prevalence of early onset type 2 diabetes rises globally, our findings highlight an opportunity to re-evaluate treatment paradigms and support scalable implementation of integrated dietary and exercise interventions for remission. Our approach may be particularly valuable in those seeking or with potential for pregnancy. It warrants further evaluation in longer term studies in real-world settings."
