Low-Calorie Diet, Exercise Reversed Type 2 Diabetes Without Meds

A low-calorie diet and exercise reversed early-onset type 2 diabetes for more than half of young adults, the randomized RESET for Remission trial showed.

Among 96 participants, the intervention put diabetes into remission for 54% at 24 weeks, bringing HbA1c below 6.5% without glucose-lowering medications for at least 12 weeks, compared with a 4% remission rate in the usual care group (adjusted OR 21.6, 95% CI 6.2-114.5).

The intervention featured an 800-900 calorie daily meal-replacement diet, twice-weekly supervised aerobic and resistance exercise, and once-weekly independent exercise for 12 weeks. Participants then transitioned into a 12-week maintenance phase featuring a nutritionally optimized diet, tapering of meal replacements, and independent exercise.

Remission rates were consistent in subgroup analyses by sex, ethnicity, and study country, Kaberi Dasgupta, MD, MSc, of McGill University in Montreal, said at the European Association for the Study of Diabetes (EASD) annual meeting in Milan.

The findings were simultaneously published in Lancet Regional Health Americas.

Prior studies have established low-energy meal replacement diets as effective non-surgical tools for diabetes remission. However, few studies have evaluated this approach combined with structured, supervised exercise.

“It’s already quite a lot to ask someone to adhere to a meal-replacement diet,” Dasgupta said. “Adding supervised exercise makes it even more challenging. Will they be able to do it? The nice thing is, if they can do it, they stand to have the benefits of the low-energy diet — the weight loss and the remission — and perhaps also the benefits of exercise.”

Many could do it. Indeed, 90% of participants completed their final assessment. “Even though it was a big ask, people liked it, they liked the exercise, and they stayed in the study,” Dasgupta noted, adding that non-completers were assumed not to have achieved remission.

The open-label trial randomized participants 1:1 to either the intervention or routine clinical care. Eligible adults were ages 18 to 45 (average 38), had been diagnosed within the prior 6 years, and had a baseline HbA1c between 6.5% (or 6.0% if taking medication) and 10.0% (mean 7.2%). At baseline, 74% of participants were taking metformin, 20% an SGLT2 inhibitor, and a small minority a GLP-1 drug.

The study focused on those with early-onset type 2 diabetes, defined as onset prior to age 45, marked by rapid deterioration in glucose levels and increased risk of premature complications.

“Those complications can hit when they’re about to start a family, start a relationship, start a job — it’s very inconvenient, and it causes a lot of suffering,” Dasgupta emphasized.

Study co-investigator Thomas Yates, PhD, of the University of Leicester in England, highlighted how these findings contrast with current anti-obesity medications like GLP-1 drugs: “We know that these therapies produce substantial weight loss, … but 25% to 45% of weight loss with therapies comes from lean mass.”

When compared with tirzepatide (Mounjaro) in SURPASS-3, the RESET trial showed less overall weight loss (16.5 lb at 24 weeks vs 28.4 lb at 52 weeks) but greater reductions in visceral fat and liver fat fraction. “It’s really important when we’re talking about exercise that we look beyond total weight, … because that is what’s going to be driving the metabolic benefits,” Yates added.

Whole-body MRI scans revealed improvements in pancreatic fat fraction, abdominal and thigh subcutaneous fat, abdominal and thigh intermuscular fat, and thigh intramuscular fat.

Intervention participants also demonstrated greater improvements in handgrip strength, depression symptoms, diabetes distress, quality of life, blood pressure, resting heart rate, triglyceride levels, and cardiac geometry. Also, more participants in the intervention group achieved hypertension remission compared with controls (56% vs 27%).

No serious adverse events were reported. Common effects included transient diet-initiation symptoms including headaches, constipation, dizziness, and fatigue, plus a slightly higher rate of mild infections in the intervention arm.

“Because it was a two-arm study, we need further research to confirm the added benefit of exercise,” Yates concluded.