Semaglutide Injection Once-Weekly for Weight Management in Adults: Results From A Randomized Phase III, Active-Controlled Study.

AIM: To evaluate and compare the efficacy, safety, and immunogenicity of a synthetic semaglutide injection (Test semaglutide) with Wegovy (Reference semaglutide) injection for weight management. MATERIALS AND METHODS: This randomized, Phase III, non-inferiority study included adults with obesity or overweight with or without comorbidities from 21 centers in India. A total of 270 patients with body mass index ≥ 30 kg/m or ≥ 27 kg/m with the presence of at least one of the weight-related comorbidities (hypertension, dyslipidemia or type 2 diabetes mellitus) were randomized (2:1) to receive either Test semaglutide (N = 177) or Reference semaglutide injection (N = 90) once weekly with dose escalation from 0.25 to 2.4 mg. The primary endpoint was percentage change in bodyweight from baseline to Week 24. RESULTS: Out of 267 randomized patients, 246 completed the study. At Week 24, mean percent weight change from baseline was -13.8% ± 4.28% in Test and -14.1% ± 4.11% in Reference groups with least-squares mean difference of 0.26% (95% CI: -0.86% to 1.39%), meeting the criterion for non-inferiority. The proportion of patients with ≥ 5% and ≥ 10% weight loss were 96.40% and 80.60% in Test, and 98.80% and 80.00% in Reference groups, respectively at Week 24. Improvements in body mass index, waist circumference, SF-36 total score, and glycemic parameters were comparable between groups. Treatment-emergent adverse events were reported in 72.30% and 76.70% in the Test and Reference groups, respectively, with gastrointestinal events being the most common. CONCLUSIONS: Test synthetic semaglutide was found to be non-inferior to Reference semaglutide in weight management with or without comorbidities. TRIAL REGISTRATION: Prospectively registered on the Clinical Trials Registry-India, CTRI/2025/04/085487 [Registered on: 24/04/2025], https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTIwNjMx&Enc=&userName=.