Comparative Efficacy and Safety of Once-Weekly Semaglutide Formulations in Indian Adults With Obesity: A Phase III, Randomized Non-inferiority Active-Controlled Study (Size Plus Study).

INTRODUCTION: Obesity is highly prevalent in India, creating an urgent need for effective management interventions. The study hypothesizes that synthetic semaglutide has comparable safety and efficacy to the innovator drug when used in obese adults for weight management. METHODS: A phase III multicenter randomized active-controlled non-inferiority trial enrolled adults with obesity across 19 centers in India. Subjects were randomized to the test arm receiving synthetic semaglutide (Alkem Laboratories Limited) or the reference arm administered with innovator semaglutide (Wegovy®, Novo Nordisk) over 24 weeks in a 2:1 ratio. The primary efficacy endpoint was the percentage change in body weight,24 weeks post-intervention. Synthetic semaglutide was established to be non-inferior if the lower bound of the one-sided 97.5% confidence interval for the between-group difference did not exceed 4.5%. RESULTS: Of the 249 randomized participants, 246 (98.8%) completed the study. Mean percentage weight loss after 24 weeks was -14.39 ± 4.17% in the test arm and -14.61 ± 4.36% in the reference arm. The least square-mean difference was 0.15% (-0.93 to 1.24), meeting the predefined non-inferiority criterion. Weight loss >10% was achieved by 86.67% (n=143) in the test arm and 83.95% (n=68) in the reference arm (p = 0.5666), while >15% weight loss occurred in 38.79% (n=64) and 40.74% (n=33), respectively (p = 0.7683). Mean body mass index decreased by -4.93 ± 1.43 kg/m² in the test arm and -5.00 ± 1.50 kg/m² in the reference arm (p = 0.7128). Treatment-emergent adverse events were reported in 55.42% (n=92) of test-arm participants and 54.22% (n=45) of reference-arm participants. CONCLUSIONS: Test semaglutide demonstrated non-inferior efficacy, comparable safety, and similar tolerability to the innovator product.