Combining a low‑energy diet (LED) with a structured exercise programme yields a higher remission rate in individuals with early-onset type 2 diabetes (T2D) than usual care alone, according to the RESET for Remission trial presented at EASD 2026.
At 24 weeks, more than half (54 percent) of participants in the intervention group achieved the primary outcome of T2D remission compared with only 4 percent in the control group (adjusted odds ratio, 21.6). [EASD 2026, abstract 1291]
In this study, T2D remission was defined as achieving an HbA1c <6.5 percent without using glucose-lowering medications in the preceding 12 weeks, in accordance with the international consensus definition.
The remission rates were consistent across all prespecified subgroups, including sex, ethnicity, and country.
“Our remission rates are at the upper end of those reported in the literature for trials of similar duration, reinforcing the potential of structured lifestyle interventions to support clinically meaningful remission. This demonstrates, for the first time, that such effects can be achieved in a multiethnic population with early-onset T2D through a combined LED and structured exercise intervention,” the researchers noted in the published paper. [The Lancet Regional Health – Americas 2026;doi:10.1016/j.lana.2026.101664]
Secondary outcomes
At week 24, participants in the intervention group also achieved greater weight loss (between-group difference, –7 percent) and DXA*-assessed fat mass loss (between-group difference, –16.5 percent) than those in the control group.
In addition, the intervention group had reductions in liver (–9.1 percent) and pancreatic (–1.3 percent) fat fractions. These reductions provide further support for the twin-cycle hypothesis, which frames T2D as a self-perpetuating cycle of hepatic fat accumulation that triggers insulin resistance and hyperglycaemia. [Cell Metab 2018;28:547–556.e3] “[These] meaningful absolute reductions … alongside lowering of circulating triglycerides are consistent with breaking this deleterious metabolic cycle,” the investigators said.
Reductions in intramuscular (–17.6 percent) and intermuscular (–11.2 percent) thigh adipose tissue were also observed in the intervention group, which, according to the investigators, were consistent with improvements in muscle quality. Improving muscle quality and function is particularly relevant in early-onset T2D, given its prolonged lifetime burden of complications. [Ther Adv Chronic Dis 2014;5:234–244; Nat Rev Endocrinol 2020;16:321–331; Lancet 2025;405:2341–2354] Importantly, fat-free mass did not differ significantly between groups.
With regard to cardiorespiratory fitness and cardiac structure, the intervention group demonstrated a sustained increase in cardiorespiratory fitness relative to body mass (10.3 percent), along with greater improvements in HbA1c, blood pressure, resting heart rate, and triglycerides than the control group.
More than half of the participants in the intervention group achieved hypertension remission at both 12 and 24 weeks (63 percent and 56 percent, respectively). In the control group, only 13 percent and 27 percent, respectively, achieved this endpoint.
This intervention group reported more adverse events (AEs) than the control group, with the most common being headache, constipation, dizziness, and fatigue, all well-known side effects of LED. Other AEs that occurred more frequently in the intervention group were upper respiratory tract infection and COVID-19 infection. Neither group reported serious AEs.
An appealing therapeutic goal
Early-onset T2D, typically diagnosis at ≤45 years of age, has a more aggressive disease course than later-onset disease, with rapid deterioration in glucose control and an increased risk of premature complications and mortality. [Ther Adv Chronic Dis 2014;5:234–244]
“Individuals who develop T2D before the age of 45 years are likely to require many years of pharmacotherapy,” noted Prof Kaberi Dasgupta from McGill University and Research Institute of the McGill University Health Centre, Montreal, Canada, at EASD 2026.
Achieving T2D remission without glucose-lowering medication is an appealing therapeutic goal. [Diabetes Care 2021;44:2438–2444] “Some individuals simply want a nonpharmacological option [to achieve T2D remission],” Dasgupta added.
To address this, the investigators sought to determine whether a combination of a structured aerobic and resistance programme with an LED can improve outcomes without compromising remission rates.
Dasgupta and colleagues conducted a prospective, open-label, blinded-endpoint efficacy trial involving 96 adults (mean age 38 years, 47 percent female) with obesity (mean BMI 35.2 kg/m2) and early-onset T2D (mean HbA1c 7.2 percent) diagnosed within the past 6 years and not receiving insulin therapy. Participants were randomized to receive either usual care (n=46) or an LED plus structured exercise (n=50).
The intervention consisted of an LED utilizing total meal replacements (800–900 kcal/day) combined with supervised aerobic and resistance training twice weekly and an independent exercise session once weekly during weeks 1–12 (intensive phase), followed by a nutritionally optimized weight-maintenance diet alongside independent home- or gym-based exercise during weeks 13–24 (maintenance phase).
Holistic benefits
“Our findings demonstrate the feasibility and efficacy of combining structured aerobic and resistance exercise with LED for early-onset T2D, supporting its potential to deliver substantial and holistic health and well-being benefits alongside diabetes remission,” the researchers said.
“By focusing specifically on early-onset T2D, the trial addresses a growing clinical population, characterized by elevated cardiovascular disease risk, a greater cumulative complication burden, and poor long-term outcomes,” they noted.
“Overall, RESET for Remission demonstrated that in early-onset T2D, 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,” Dasgupta concluded.
“As the prevalence of early-onset T2D rises globally, our findings highlight an opportunity to re-evaluate treatment paradigms and support scalable implementation of integrated dietary and exercise interventions for remission,” the researchers added. “Our approach warrants further evaluation in longer term studies in real-world settings.”