Background: Obesity is a chronic disease with unmet needs beyond weight reduction. Survodutide, an investigational glucagon receptor/glucagon-like peptide-1 receptor dual agonist, previously reduced body weight in adults with obesity without type 2 diabetes (T2D).
Methods: SYNCHRONIZE-1 (NCT06066515) was a multinational, randomised, double-blind, phase 3 trial in adults aged ≥18 years with a body mass index (BMI) ≥30 kg/m² or ≥27 kg/m² with at least one obesity complication, excluding T2D. Participants were randomised 1:1:1 to survodutide 3.6 mg, survodutide 6.0 mg, or placebo for 76 weeks. Primary endpoints were percent change in body weight (BW) and achievement of a ≥5% BW reduction from baseline to Week 76. Secondary endpoints included cardiometabolic and body composition outcomes. Safety was assessed by adverse events.
Results: A total of 726 participants were randomised across 116 sites in 14 countries. At Week 76, mean percent BW change using the efficacy estimand was −15.3% with survodutide 3.6 mg, −16.6% with survodutide 6.0 mg, and −3.2% with placebo; corresponding changes using the treatment-regimen estimand were −12.2%, −13.0%, and −5.4%. Body weight reduction of ≥5% was achieved by 83.8%, 85.1%, and 38.8% of participants, respectively. Survodutide was also associated with reductions in systolic blood pressure of up to 7.9 mmHg and glycated haemoglobin of up to 0.3%. In a descriptive on-treatment analysis, up to 78.9% of participants with prediabetes achieved normoglycaemia at Week 76 versus 20.0% with placebo. In a prespecified magnetic resonance imaging subset, survodutide reduced total body fat by ~28%, visceral fat by ~34%, and liver fat by ~63%, versus 9%, 12%, and 24% with placebo, respectively. Gastrointestinal events were the most common adverse events and were mild-to-moderate and non-serious.
Conclusion: In adults with obesity without T2D, survodutide produced relevant BW reductions and improvements in cardiometabolic and adiposity measures, including liver fat, without new safety concerns.