Novel Semaglutide Injection Non-Inferior to Reference Biologic for Glycemic Control in Indian Type 2 Diabetes Mellitus Patients

Type 2 Diabetes Mellitus (T2DM) is a major health challenge in India, affecting over 89.8 million adults. Long-acting GLP-1 receptor agonists (GLP-1RAs) are established for improving glycemic control and offering cardiovascular benefits, yet access to these advanced therapies can be limited by cost and availability. This Phase 3 trial aimed to evaluate a novel semaglutide injection developed by Zydus Lifesciences Ltd., comparing its efficacy and safety against the reference biologic, specifically addressing the need for accessible treatment options for Indian adults with T2DM inadequately controlled on metformin.

In this multicentre, randomized, active-controlled Phase 3 study, 314 Indian adults (aged 18-65 years, HbA1c 7.0-10.5%) with Type 2 Diabetes Mellitus inadequately controlled on metformin were randomized 1:1. Participants received either a novel semaglutide injection (test arm) or reference semaglutide once-weekly for 24 weeks. Doses were titrated according to glycaemic targets. The primary endpoint was the change in HbA1c at 24 weeks, with a pre-specified non-inferiority margin of 0.4 percentage points. Secondary endpoints included changes in body weight, BMI, fasting and post-prandial glucose, lipid profile, blood pressure, and safety profile. Analyses were conducted on the modified intent-to-treat (mITT) population.

The novel semaglutide injection demonstrated non-inferiority to the reference biologic in glycemic control.

HbA1c decreased from 8.36% to 6.81% in the test group and from 8.36% to 6.79% in the comparator, with a least-squares mean difference of -0.0038% (95% CI -0.20 to 0.19), successfully meeting the pre-specified non-inferiority margin. Reductions in body weight were comparable (-4.59 kg vs -4.42 kg), as were BMI (-1.76 kg/m2 vs -1.68 kg/m2), fasting plasma glucose (-37.5 mg/dL vs -39.0 mg/dL), and post-prandial plasma glucose (-54.5 mg/dL vs -55.7 mg/dL) at week 24. Treatment-emergent adverse events (TEAEs) occurred in 58.6% of patients in the test group and 61.8% of patients in the comparator group, predominantly mild with no serious adverse events reported. Hypoglycemia was infrequent and mild (1.9% vs 0%). Anti-drug antibodies were detected in 2.23% of samples, indicating low immunogenicity.