Survodutide Once Weekly in Adults with Obesity and Type 2 Diabetes

BackgroundFor persons living with both type 2 diabetes and obesity, weight management may be the most effective therapy for type 2 diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists have potent weight-reducing effects, and other mechanisms may confer additional benefits. Survodutide is an investigational glucagon receptor–GLP-1 receptor dual agonist with potential weight-reducing and metabolic benefits. MethodsIn this multinational, double-blind, phase 3 trial involving adults with type 2 diabetes and a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 27 or more, we randomly assigned participants in a 1:1:1 ratio to receive once-weekly subcutaneous survodutide (3.6 mg or 6.0 mg) or placebo. The two primary end points were the percent change in body weight and a reduction in body weight of at least 5% from baseline to week 76. ResultsAmong 752 participants (250 in the 3.6-mg survodutide group, 251 in the 6.0-mg survodutide group, and 251 in the placebo group), the mean age at baseline was 55.7 years, and the mean BMI was 36.5; 49.3% were men. The mean weight change at week 76 according to the treatment-regimen estimand (which assessed effects regardless of whether the trial regimen was discontinued or interrupted or whether other antiobesity therapies were used) was –8.2% (95% confidence interval [CI], −9.2 to −7.2) in the 3.6-mg group, –9.8% (95% CI, −10.8 to −8.8) in the 6.0-mg group, and –3.9% (95% CI, −4.9 to −2.9) in the placebo group; weight reduction of at least 5% occurred in 57.6%, 64.5%, and 35.1% of the participants, respectively (P<0.001 for all comparisons with placebo). The mean change in the glycated hemoglobin level (from a baseline level of 7.4%) was –0.9 percentage points in the 3.6-mg group, –0.8 percentage points in the 6.0-mg group, and –0.2 percentage points in the placebo group. The most common adverse events were gastrointestinal (generally mild to moderate and transient), which occurred in 182 participants (72.8%) in the 3.6-mg group, 195 (77.7%) in the 6.0-mg group, and 97 (38.6%) in the placebo group. ConclusionsIn adults with obesity and type 2 diabetes, survodutide at a weekly dose of 3.6 mg or 6.0 mg resulted in significantly greater weight reduction than placebo. (Funded by Boehringer Ingelheim; SYNCHRONIZE-2 ClinicalTrials.gov number, NCT06066528.)