Half of Young Adults in RESET Put Type 2 Diabetes in Remission

Type 2 diabetes diagnosed before 45 carries a high lifetime risk of complications, simply because people who get it young have more years for damage to build. A trial published on October 1 in The Lancet Regional Health Americas tested whether that early disease can be pushed into remission without medication, and found that it could in more than half of participants within six months. The trial, called RESET for Remission, combined a very low calorie diet with supervised exercise, a pairing earlier remission trials had not tested.

A second study, presented at the EASD meeting in Milan at the end of September, supplies the reason this matters: what tends to happen in the years after a type 2 diagnosis when the disease is simply managed.

What RESET tested

Kaberi Dasgupta of McGill University and colleagues at the Leicester Diabetes Centre and the University of Alberta randomized 96 adults aged 18 to 45 with early onset type 2 diabetes and obesity, none on insulin. Their mean age was 38 and their mean body mass index 35.2. Forty were in the United Kingdom and 56 in Canada.

The intervention group spent 12 weeks on a meal replacement diet of 800 to 900 kilocalories a day, with two supervised exercise sessions a week combining aerobic and resistance training, plus one session on their own. For the next 12 weeks they moved to a weight maintenance diet and continued exercising independently. The control group received usual care. The primary outcome was remission at 24 weeks: HbA1c below 6.5% without any glucose lowering medication for at least 12 weeks.

The results

Remission occurred in 27 of 50 people in the intervention group (54%) and 2 of 46 on usual care (4%), a difference of 50 percentage points. After adjustment, the intervention group had about 21 times the odds of remission, though with a wide confidence interval, from 6.2 to 114.5, as expected in a trial this size. The effect was consistent across sex and ethnicity. Ninety percent of participants attended the final assessment.

The body composition results set this trial apart. Rapid weight loss often costs muscle along with fat. Here, the intervention reduced fat mass by 16.5% relative to the control group with no change in fat free mass, and imaging showed preserved muscle volume and less fat inside muscle. Handgrip strength rose, fitness relative to body weight improved by 10.3%, and resting blood pressure and heart rate fell. Depressive symptoms and diabetes distress decreased.

Most people in the intervention group (43 of 50) had at least one side effect, against 6 of 46 controls, mostly early effects of the diet such as constipation, headache, dizziness and fatigue that resolved. There were no serious adverse events.

What waiting costs

The EASD study, led jointly by Naveed Sattar of the University of Glasgow, used data from CALOR, an observational program sponsored by AstraZeneca. It followed 1,617,508 Americans newly diagnosed with type 2 diabetes between 2010 and March 2024. Their average age at diagnosis was 59, and 51% were women. Most already carried other risks: 72% had abnormal blood fats and 68% high blood pressure.

Within five years of diagnosis, the combined risk of developing chronic kidney disease or heart failure, or dying, was 33%. By ten years it was 55%. Kidney disease usually came first: the five year risk of chronic kidney disease as the first complication was 19.0%, against 8.3% for heart failure. One complication also led to the other. Among people who developed heart failure first, 42% developed kidney disease within the next five years; among those with kidney disease first, 23% went on to heart failure.

These figures describe an older population than RESET's, and an observational study cannot say how many of those events better treatment would prevent. The release also notes possible selection bias. But the direction is clear, and for people diagnosed at 38 rather than 59, there are two more decades of exposure for the same trajectory to unfold.

Why this trial matters now

Much of the current attention in diabetes goes to GLP-1 drugs, and for good reason. RESET is a reminder that a structured program without drugs can still produce remission in half of young patients within six months, and that adding resistance training appears to protect the muscle that rapid weight loss often takes. Muscle loss is the same problem drug developers are now trying to solve with add on antibodies, as we covered in our piece on keeping muscle on GLP-1 drugs.

The open question is durability. Remission at six months is a beginning, not an outcome. A longer trial, with a diet only comparison, would tell whether supervised exercise is the ingredient that makes the difference. Given that the alternative trajectory for these patients runs toward a one in three chance of kidney disease, heart failure or death within five years, that trial deserves funding quickly.