Research Summary

Survodutide Reduces Weight in International Phase 3 Obesity Trial

Edited by:
Ashton L. Stahl

Key Highlights

  • Survodutide significantly reduced body weight compared with placebo at 76 weeks.
  • At least 5% weight reduction occurred in approximately 72% of survodutide-treated participants.
  • Gastrointestinal events were common and led to treatment discontinuation in up to 20.2% of participants receiving survodutide.

Once-weekly survodutide produced significantly greater reductions in body weight than placebo among adults with obesity without diabetes, according to findings from the international phase 3 SYNCHRONIZE-1 trial published in The New England Journal of Medicine. Survodutide is an investigational dual agonist of the glucagon and glucagon-like peptide-1 receptors.

The 76-week, double-blind, placebo-controlled trial was conducted at 116 clinical sites across 14 countries. Researchers randomly assigned participants in a 1:1:1 ratio to receive once-weekly subcutaneous survodutide at 3.6 mg, 6 mg, or placebo. All participants also received counseling on a reduced-calorie diet and increased physical activity.

Eligible adults had a BMI of at least 30 or at least 27 with 1 or more obesity-related complications, excluding diabetes. The 2 primary endpoints were the percentage change in body weight and the proportion of participants achieving at least a 5% weight reduction from baseline to week 76.

Study Findings

The modified intention-to-treat population included 725 participants: 241 in the 3.6-mg group, 242 in the 6-mg group, and 242 in the placebo group. Their mean age was 47.1 years, mean BMI was 37.9, and mean body weight was 108.8 kg.

At week 76, mean body weight decreased by 12.2% with survodutide 3.6 mg, 13% with survodutide 6 mg, and 5.4% with placebo. The respective differences from placebo were −6.8 percentage points and −7.5 percentage points (P < .001 for both comparisons).

At least 5% weight reduction occurred in 72.6% of participants receiving survodutide 3.6 mg, 71.9% receiving survodutide 6 mg, and 46.3% receiving placebo. Weight reductions of at least 20% occurred in 24.9%, 28.5%, and 6.6% of participants, respectively.

Gastrointestinal disorders occurred in 80.9% of the 3.6-mg group, 89.7% of the 6-mg group, and 47.9% of the placebo group. These events were generally mild to moderate but led to treatment discontinuation in 17.8%, 20.2%, and 2.9% of participants, respectively. No deaths were reported.

Clinical Implications

According to the study authors, weight reduction with survodutide was accompanied by reductions in cardiometabolic risk factors and improvements in body composition and liver health markers.

The authors noted that the trial lacked an active comparator and that a substantial proportion of participants discontinued the assigned regimen. They also cited the exclusion of adults with uncontrolled hypertension, recent cardiovascular events, or inadequately controlled mood disorders and noted that weight reduction in the placebo group exceeded expectations.

Expert Commentary

“In this trial, once-weekly survodutide led to significantly greater reductions in body weight than placebo in adults with obesity,” the researchers concluded.

Reference

le Roux CW, Wharton S, Startseva E, et al. Survodutide once weekly for the treatment of adults with obesity. N Engl J Med. 2026;395(8):776-787. doi:10.1056/NEJMoa2600751