Survodutide led to significant weight loss in adults with obesity and without diabetes, according to results from the randomized, placebo-controlled SYNCHRONIZE-1 trial published June 7 in NEJM.

This phase 3, double-blind trial randomly assigned adults with a BMI >30 or >27 plus one or more obesity-related complication (excluding diabetes) 1:1:1 to receive once-weekly survodutide administered subcutaneously at a dose adjusted up to 3.6mg, 6.0mg or placebo. Participants also underwent counseling for lifestyle modification during the trial, which was conducted across 116 sites in 14 countries from November 2023 through February 2026.

Carel Le Roux, MD, et al., defined the two primary endpoints as the percent change in body weight, and at least a 5% reduction in body weight from baseline to 76 weeks. Notably, primary efficacy analysis was based on the treatment-regimen estimand, accounting for factors such as early discontinuation of survodutide or placebo, use of prohibited obesity medications, and extended dose-escalation periods.

At baseline, mean BMI was 37.9 and mean body weight was 108.8 kg for the 725 study participants (mean age of 47 years, 41% men, 68% White).

At week 76, participants' mean change in body weight from baseline was –12% in the 3.6 mg group, –13% in the 6.0 mg group and –5% in the placebo group. Additionally, 73%, 72% and 46% of the participants, respectively, had weight reduction of at least 5% (p≤0.0001 for all comparisons with placebo).

No deaths were reported, and the most common adverse events were mild to moderate gastrointestinal symptoms which occurred in 81% of the participants in the 3.6 mg group, 90% in the 6.0 mg group and 48% in the placebo group.

Despite study limitations including the lack of an active comparator, discontinuation of the trial regimen by a substantial percentage of the participants and the exclusion of participants with uncontrolled hypertension, study authors note that "the safety profile of survodutide in this trial appeared to be consistent with those of other obesity medications with GLP-1 receptor agonist activity..."

"Survodutide led to significantly greater reductions in body weight than placebo in adults with obesity without diabetes," they write.