Phase 3 trial of survodutide for overweight/obesity meets coprimary endpoints
ADA 2026 – In SYNCHRONIZE-1 among patients with overweight or obesity but no T2D, survodutide reduced body weight up to 13% at 76 weeks compared with placebo, and almost three-quarters of the participants lost ≥5%. There were no new safety concerns.
This summary is based on the presentation of Carel le Roux, PhD (Dublin, Ireland) at the ADA Scientific Sessions 2026 - Efficacy and Safety of Survodutide for the Treatment of Obesity in People without Diabetes: Results from SYNCHRONIZE-1.
Introduction and methods
The introduction of GLP-1RAs has changed the management of obesity. New compounds are being investigated that have complementary mechanisms of actions, such as the dual glucagon/GLP-1 receptor agonist survodutide. In a recent phase 2 trial, survodutide treatment showed significant, dose-dependent weight reductions compared with placebo after 46 weeks in patients with overweight or obesity but no diabetes.
In the SYNCHRONIZE-1 trial, a global, multicenter, double-blind, placebo-controlled, phase 3 RCT, the efficacy and safety of survodutide were assessed in 725 patients with BMI ≥30 kg/m² or ≥27 kg/m² with ≥1 obesity-related complication, but with no T2D. Participants were randomized in a 1:1:1 ratio to subcutaneous survodutide (3.6 or 6.0 mg) or placebo once weekly for 76 weeks, in addition to counseling for lifestyle modification.
The coprimary endpoints were the percentage change in body weight and achievement of body weight reduction ≥5%, both measured from baseline to 76 weeks. Secondary endpoints included changes in waist circumference, blood pressure, HbA1c levels, and liver fat content (LFC).
Main results
- In the intention-to-treat analysis, the mean relative change in body weight from baseline to 76 weeks was –12.2% (95%CI: −13.6% to −10.8%) in patients treated with survodutide 3.6 mg (n=241), –13.0% (95%CI: −14.4% to −11.6%) in those receiving survodutide 6.0 mg (n=242), and –5.4% (95%CI: −6.9% to −4.0%) in those receiving placebo (n=242) (P<0.001 for both comparisons with placebo).
- At 76 weeks, a body weight reduction ≥5% from baseline was observed in 72.6%, 71.9%, and 46.3% of the participants receiving survodutide 3.6 mg, survodutide 6.0 mg, or placebo, respectively (P<0.001 for both comparisons with placebo).
- The secondary endpoints were analyzed in a per-protocol analyses. As for the key secondary endpoint waist circumference, the adjusted mean was reduced by 13.1 cm in the survodutide 3.6-mg group from baseline to 76 weeks, by 14.6 cm in the survodutide 6.0-mg group, and by 4.6 cm in the placebo group.
- The survodutide groups showed a similar decrease in adjusted mean systolic blood pressure over 76 weeks (3.6 mg: –7.9 mmHg; 6.0 mg: –7.5 mmHg), whereas the decline in the placebo group was smaller (–3.2 mmHg).
- The baseline HbA1c level was 5.5% in all 3 study arms. At 76 weeks, the absolute HbA1c change was –0.26% in the survodutide 3.6-mg group, –0.27% in the survodutide 6.0-mg group, and 0.07% in the placebo group.
- Survivotide treatment also appeared to improve the lipid profile over time, as indicated by larger decreases in total cholesterol, LDL-c, and triglyceride levels compared with placebo.
- The frequency of adverse events was 96.9% in the combined survodutide groups and 86.0% in the placebo group.
- The most common adverse events were gastrointestinal symptoms (mostly mild to moderately severe), which occurred in 80.9% of the participants in the survodutide 3.6-mg group, 89.7% of those in the survodutide 6.0-mg group, and 47.9% of those in the placebo group.
- There were no reported deaths.
- An MRI substudy indicated survodutide improved body composition, mainly by reducing fat tissue, and decreased LFC compared with placebo.
Conclusion
In the SYNCHRONIZE-1 trial, 76-week treatment with survodutide led to sustained body weight reductions up to 13% compared with placebo in patients with overweight or obesity but no T2D. Almost three-quarters of the survodutide-treated participants lost ≥5% of their body weight, compared with 46% of the placebo-treated patients. There were also indications that survodutide reduced visceral and liver fat and improved glucose and lipid metabolism. No new safety concerns were reported.
- Our reporting is based on the information provided at the ADA Scientific Sessions 2026 and publication of the data in The New England Journal of Medicine -