Phase 3 Trial Finds Greater Weight Reduction With Survodutide in Adults With Obesity and Type 2 Diabetes

Once-weekly subcutaneous survodutide (Boehringer Ingelheim), an investigational glucagon receptor–glucagon-like peptide-1 (GLP-1) receptor dual agonist, produced significantly greater weight reduction than placebo in adults with obesity and type 2 diabetes, according to phase 3 results published in NEJM.

The double-blind SYNCHRONIZE-2 trial, conducted at 133 clinical sites in 19 countries and funded by Boehringer Ingelheim, evaluated survodutide as an adjunct to a reduced-calorie diet and increased physical activity. The investigators noted that obesity medications are typically less efficacious in persons with type 2 diabetes.

The trial randomly assigned adults with type 2 diabetes and a body-mass index (BMI) of 27 or more in a 1:1:1 ratio to survodutide 3.6mg, survodutide 6.0mg, or placebo. Among 752 participants, the mean age was 55.7 years and the mean BMI was 36.5. At week 76, the mean change in body weight according to the treatment-regimen estimand was −8.2% with 3.6mg, −9.8% with 6.0mg, and −3.9% with placebo (P<0.001 for both doses vs placebo). The second primary end point, weight reduction of at least 5%, was reached by 57.6%, 64.5%, and 35.1% of participants, respectively.

From a mean baseline of 7.4%, glycated hemoglobin levels changed by −0.9 and −0.8 percentage points in the 3.6mg and 6.0mg groups, respectively, vs −0.2 percentage points with placebo. Gastrointestinal adverse events, generally mild to moderate and transient, were the most common, occurring in 72.8%, 77.7%, and 38.6% of the 3.6mg, 6.0mg, and placebo groups, respectively. These events led to discontinuation of the trial regimen in 18.0%, 17.9%, and 1.2%. Hypoglycemia occurred in 8.0%, 9.2%, and 4.0%.

The investigators described excluding people taking insulin as an important limitation that restricts generalizability to the wider type 2 diabetes population, as does the reasonable baseline glycemic control of most participants. They also noted that the trial was not designed to evaluate potential long-term effects on cancer risk; the separate SYNCHRONIZE-CVOT trial is investigating cardiovascular outcomes.

Source: Wharton S, le Roux CW, Startseva E, et al. Survodutide once weekly in adults with obesity and type 2 diabetes. N Engl J Med. Published October 1, 2026. doi:10.1056/NEJMoa2607219