Efficacy and safety of novel formulation of semaglutide injection: A multicentre, randomized, comparative, active controlled, phase 3 study in comparison with reference biologic in Indian patients with type 2 diabetes mellitus

Abstract

Background

Type 2 diabetes mellitus (T2DM) is the most common non-communicable disease affecting over 89.8 million adults in India. Evidence suggests long-acting glucagon-like peptide-1 (GLP-1) receptor agonist improves glycaemic control in the patients with T2DM. This phase 3 trial compared a novel semaglutide injection developed by Zydus Lifesciences Ltd. with the reference biologic in Indian adults with T2DM inadequately controlled on metformin.

Methods

In this multicentre, randomised study, 314 patients aged 18–65 years with HbA1c 7.0–10.5 % were randomised 1:1 to once-weekly semaglutide injection (test) or reference semaglutide for 24 weeks. Doses were titrated according to glycaemic targets. The primary endpoint was change in HbA1c at 24 weeks (pre-specified non-inferiority margin of 0.4 percentage points). Secondary endpoints included changes in fasting and post-prandial glucose, body weight, BMI, lipid profile, blood pressure, rescue medication use, safety profile and anti-drug antibody formation. Analyses were conducted on the modified intent-to-treat (mITT) population.

Results

Of 314 randomised participants, 274 completed the trial (133 in the test arm and 141 in the comparator arm). 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), meeting the pre-specified non-inferiority margin. Reductions in body weight (−4.59 vs −4.42 kg), BMI (−1.76 vs −1.68 kg/m²), fasting plasma glucose (−37.5 vs −39.0 mg/dL) and post-prandial plasma glucose (−54.5 vs −55.7 mg/dL) at week 24 were comparable between the groups. Treatment-emergent adverse events (TEAEs) were reported in 58.6 % of patients in the test group and 61.8 % of patients in the comparator group, respectively. Most events were mild and no serious adverse events occurred. Hypoglycaemia was infrequent and mild (1.9 % vs 0 %). Anti-drug antibodies were detected in 2.23 % of samples and had no impact on efficacy.

Conclusions

This novel formulation of once-weekly semaglutide injection demonstrated non-inferior glycaemic efficacy, safety & immunogenicity to the reference product in Indian adults with type 2 diabetes.

Trial registration

Clinical Trials Registry–India (CTRI/2025/03/082615).