Expanding access to glucagon-like peptide-1 receptor agonist therapy remains an important consideration in type 2 diabetes mellitus (T2DM), particularly with increasing demand for semaglutide-based treatment. A phase III, randomized, open-label, active-controlled noninferiority trial published in Diabetes, Obesity and Metabolism compared a synthetic semaglutide injection with reference semaglutide in adults with T2DM in India.

The multicenter study enrolled adults aged 18 to 65 years with HbA1c levels between 7.0% and 10.5% despite stable metformin therapy and lifestyle management. Participants were randomized 1:1 to receive once-weekly subcutaneous synthetic semaglutide or reference semaglutide for 24 weeks using an identical dose-escalation regimen from 0.25 mg to 2.0 mg weekly. The primary endpoint was change in HbA1c from baseline to week 24. A total of 314 patients were randomized, and 290 completed the study.

Findings

• HbA1c decreased significantly in both groups at week 24 (synthetic semaglutide: −2.04%; reference semaglutide: −1.95%; both P<0.0001 within groups).
• The least-squares mean difference between groups was −0.09% (95% CI −0.26 to 0.09), meeting the predefined noninferiority criterion.
• Reductions in fasting blood glucose, postprandial blood glucose, and bodyweight were similar between treatment groups.
• Rates of treatment-emergent adverse events were comparable between synthetic and reference semaglutide, with predominantly mild-to-moderate gastrointestinal events reported in 43.3% and 46.5% of patients, respectively.
• No anti-drug antibodies or neutralizing antibodies were detected during the study.

Synthetic semaglutide demonstrated glycemic efficacy and safety comparable to reference semaglutide over 24 weeks in adults with T2DM receiving metformin therapy. The findings support its potential use as an additional therapeutic option in T2DM management.