Survodutide once-weekly achieves up to 13.0% body weight reduction in adults with obesity

Despite the transformative impact of glucagon-like peptide-1 (GLP-1) receptor agonists on obesity management and cardiometabolic health, significant unmet needs persist, particularly for individuals seeking greater weight loss. Current standard-of-care GLP-1RAs, while effective, may not achieve optimal outcomes for all patients. Survodutide, an investigational dual agonist targeting both the glucagon receptor and GLP-1 receptor, is being explored for its potential to induce superior weight reductions compared to GLP-1R mono-agonists, addressing this gap in therapeutic efficacy.

This phase 3, double-blind, randomized trial enrolled 725 adults with a body-mass index (BMI) of 30 or higher, or 27 or higher with at least one obesity-related complication (excluding diabetes). Participants were randomized 1:1:1 to receive once-weekly subcutaneous survodutide at a dose adjusted up to 3.6 mg or 6.0 mg, or placebo, for 76 weeks, alongside lifestyle modification counseling. Primary endpoints were the percent change in body weight and a reduction of at least 5% from baseline to week 76. Efficacy analysis used a treatment-regimen estimand, accounting for discontinuations and protocol deviations.

Among 725 participants (mean age 47.1 years, mean baseline BMI 37.9, mean body weight 108.8 kg), survodutide demonstrated significant weight reductions compared to placebo. At week 76, the mean change in body weight from baseline was:

-12.2% (95% CI, -13.6 to -10.8) in the 3.6 mg survodutide group.

The 6.0 mg survodutide group achieved a mean reduction of -13.0% (95% CI, -14.4 to -11.6), while the placebo group saw a -5.4% (95% CI, -6.9 to -4.0) reduction. Furthermore, 72.6% of the 3.6 mg group and 71.9% of the 6.0 mg group achieved at least 5% weight reduction, compared to 46.3% in the placebo group (P<0.001 for all comparisons with placebo). The most common adverse events were gastrointestinal, consistent with this class of drugs.