AIM: To evaluate the efficacy, safety and immunogenicity of semaglutide injection (synthetic) (Test group) compared with the Reference semaglutide injection [Ozempic, (Reference group)] in Indian patients with Type 2 diabetes mellitus (T2DM).
MATERIALS AND METHODS: This Phase III, randomised, open-label, multi-centre, parallel-group, active-controlled non-inferiority study was conducted across 35 centres in India. Adults aged 18-65 years with T2DM and baseline glycated haemoglobin (HbA1c) ≥ 7.0% to ≤ 10.5% despite stable metformin therapy and diet & exercise control were randomised (1:1) to receive subcutaneous injections of Test semaglutide or Reference semaglutide once weekly for 24 weeks, using an identical dose-escalation regimen (from 0.25 to 2.0 mg per week). The primary endpoint was change in HbA1c from baseline to Week 24. Secondary endpoints included changes in fasting and post-prandial blood glucose, bodyweight and HbA1c < 7.0% achievers, safety and immunogenicity.
RESULTS: A total of 314 patients were randomised, and 290 patients completed the study. At Week 24, both treatments produced significant and comparable reductions in HbA1c (Test: -2.04%, Reference: -1.95%; p < 0.0001 within groups). The least-squares mean difference (Test-Reference) was -0.09% (95% CI: -0.26 to 0.09), meeting the pre-specified non-inferiority criterion. Improvements in fasting and post-prandial blood glucose, patients achieving HbA1c < 7.0% and bodyweight were similar between the two groups. The most common treatment-emergent adverse events were predominantly mild-to-moderate gastrointestinal events (Test vs. Reference: 43.3% vs. 46.5%). No anti-drug or neutralising antibodies were detected.
CONCLUSIONS: The Test synthetic semaglutide injection demonstrated non-inferior glycaemic efficacy, comparable safety in comparison to Reference semaglutide, supporting its use as an effective therapeutic option for patients with T2DM. Prospectively registered on the Clinical Trials Registry-India, CTRI/2025/02/080592 [Registered on: 14/02/2025], URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTIwODUw&Enc=&userName=.
