Survodutide Once Weekly for the Treatment of Adults with Obesity.
The SYNCHRONIZE-1 trial was a phase 3, double-blind, randomized controlled trial evaluating survodutide — an investigational dual glucagon receptor and GLP-1 receptor agonist — for weight management in adults with obesity (BMI ≥30, or ≥27 with an obesity-related complication) who did not have diabetes. A total of 725 participants were randomized 1:1:1 to one of two dose levels of once-weekly subcutaneous survodutide or placebo, alongside lifestyle counseling, over 76 weeks. The study found that both survodutide groups achieved significantly greater mean body weight reductions compared to placebo (-12.2% and -13.0% versus -5.4%). Approximately 72% of participants in each survodutide group achieved at least 5% body weight reduction, compared to about 46% in the placebo group. The primary analysis used a treatment-regimen estimand accounting for early discontinuations and protocol deviations. Limitations include the relatively short 76-week duration for a chronic condition, the exclusion of people with diabetes, and industry funding by Boehringer Ingelheim. Long-term cardiovascular and safety outcomes remain to be established in ongoing or future trials.
Why this grade: This is a phase 3, double-blind, placebo-controlled RCT with 725 participants across three arms, providing high-quality direct human evidence for weight outcomes with survodutide in 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 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.).
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