Survodutide Once Weekly for the Treatment of Adults with Obesity

BACKGROUND: Although medications with glucagon-like peptide-1 (GLP-1) receptor agonist activity have transformed the management of obesity and shown substantial cardiometabolic benefits, unmet needs remain. Survodutide, an investigational glucagon receptor-GLP-1 receptor dual agonist, led to substantial weight reduction in a phase 2 trial involving adults with obesity without diabetes. METHODS: In this phase 3, double-blind trial, we randomly assigned adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher, or 27 or higher with at least one obesity-related complication (excluding diabetes), in a 1:1:1 ratio to receive once-weekly survodutide administered subcutaneously at a dose adjusted up to 3.6 mg or 6.0 mg or placebo, in addition to counseling for lifestyle modification. 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. The primary efficacy analysis was conducted according to the treatment-regimen estimand, which incorporates the effects of any early discontinuation of survodutide or placebo, the use of protocol-prohibited obesity medications, and a prolonged dose-escalation period. RESULTS: Among 725 participants (241 in the 3.6-mg survodutide group, 242 in the 6.0-mg survodutide group, and 242 in the placebo group), the mean age was 47.1 years; 294 participants (40.6%) were men. At baseline, the mean BMI was 37.9, and the mean body weight was 108.8 kg. At week 76, the mean change in body weight from baseline according to the treatment-regimen estimand was -12.2% (95% confidence interval [CI], -13.6 to -10.8) in the 3.6-mg group, -13.0% (95% CI, -14.4 to -11.6) in the 6.0-mg group, and -5.4% (95% CI, -6.9 to -4.0) in the placebo group; 72.6%, 71.9% and 46.3% of the participants, respectively, had weight reduction of at least 5% (P<0.001 for all comparisons with placebo). The most common adverse events were gastrointestinal symptoms (typically mild to moderate), which occurred in 80.9% of the participants in the 3.6-mg group, in 89.7% of those in the 6.0-mg group, and in 47.9% of those in the placebo group. No deaths were reported. CONCLUSIONS: Survodutide led to significantly greater reductions in body weight than placebo in adults with obesity without diabetes. (Funded by Boehringer Ingelheim; SYNCHRONIZE-1 ClinicalTrials.gov number, NCT06066515.).