Efficacy and safety of semaglutide injection in comparison with reference semaglutide for chronic weight management in indian adults with obesity: A phase III randomized non-inferiority trial.

BACKGROUND: In India, approximately 33-46% people are obese which is a major risk factor to several non-communicable diseases. Amongst all existing treatment modalities, semaglutide injection is the proven most effective glucagon-like peptide-1 (GLP-1) receptor agonist for obesity, but high costs limit global accessibility. We report the Phase III trial evaluating the efficacy, safety and immunogenicity of a novel formulation of Semaglutide Injection in Indian patients with obesity. METHODS: This multicentre, randomized, open-label, active-controlled trial enrolled 282 Indian adults with obesity (BMI ≥30 kg/m) or overweight with comorbidities across geographically distributed 23 sites. Participants were randomized 2:1 to Semaglutide Injection 15 mg/3 mL (5 mg/mL) (Test Product; Zydus Lifesciences Ltd.) or Reference Semaglutide (0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg) prefilled pen (Comparator Product; Novo Nordisk) for 24 weeks. Both arms followed an identical dose-escalation schedule from 0.25 mg to 2.4 mg once weekly. The primary endpoint was percentage weight change, with a non-inferiority margin of 5 percentage points. RESULTS: In terms of primary endpoint, Least squares mean (LSM) was -11.25% (Test Product) versus -11.50% (reference semaglutide), with a treatment difference of 0.25% (95% CI: -0.72 to 1.23), at the end of 24 weeks confirming non-inferiority. 90.4% and 58.0% of Test Product-treated participants achieved ≥5% and ≥10% weight loss, respectively. Adverse events were similar between groups (63.3% vs 62.8%), with predominantly mild gastrointestinal symptoms. No serious treatment-related adverse events, deaths, or discontinuations occurred. CONCLUSIONS: This novel formulation of Semaglutide Injection demonstrated therapeutic non-inferiority to the reference product with comparable safety and immunogenicity. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI/2025/03/082620).