Bridging Innovation and Access: Randomized, Single-Dose, Open-Label, Parallel-Group Bioequivalence Study of Generic and Innovator Injection Semaglutide in India

Abstract

Semaglutide, a long-acting Glucagon-Like Peptide-1 (GLP-1) receptor agonist, is effective in improving glycemic control, reducing body weight, and lowering cardiovascular risk in Type 2 Diabetes Mellitus (T2DM). Limited accessibility of the innovator formulation underscores the need for bioequivalent generic alternatives. To assess the pharmacokinetic bioequivalence of a synthetic Semaglutide Injection (2 mg/1.5 mL) developed by Alkem Laboratories Ltd., India, compared with the innovator product under fasting conditions in healthy adults. This randomized, open-label, single-dose, two-arm, parallel-group bioequivalence study enrolled 80 healthy male and female volunteers (18–45 years). Participants received a single 0.5 mg subcutaneous dose of either the test or reference formulation. Plasma Semaglutide concentrations were measured up to 816 hours post-dose using a validated LC-MS/MS method. Pharmacokinetic parameters (Cmax, AUC₀₋t, AUC₀₋∞) were derived by non-compartmental analysis and statistically compared using ANOVA on log-transformed data. Bioequivalence was concluded if 90% Confidence Intervals (CI) for geometric mean ratios were within 80.00–125.00%. Seventy-five subjects completed the study and were included in the analysis. The geometric mean ratios (90% CI) were 94.60% (88.46–101.17%) for Cmax, 96.70% (91.13–102.60%) for AUC₀₋t, and 96.00% (89.76–102.67%) for AUC₀₋∞, all within regulatory bioequivalence limits. Concentration–time profiles were comparable between formulations, with no statistically significant differences (p>0.05). Both products were well tolerated, and no serious adverse events occurred. The synthetic Semaglutide Injection was pharmacokinetically bioequivalent to the innovator product and demonstrated good tolerability. These findings support its use as a cost-effective alternative that may enhance access to GLP-1-based therapy in resource-limited settings.