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).
Authors: Prabhat Kumar Sharma, V Viswaprasad, Animesh Choudhary, Ansari Rizwanahmed Nurulhasan, Sagar Vivek Redkar, Patel Manan Bharatkumar, Vijaykumar Shivajirao Patil, Sumit Anand, Vijaykumar Barge, Shalin J Shah, Chintan B Patel, Kanugula Sudheer, Shrikant Somani, Konatham Rambabu, Surya Veeramani Kartheek Adhikarla, M Swapna, Shravan Kumar Ankathi, Veer Bahadur Singh, Gouranga Sarkar, S K Gautam, Kalyan Kumar Das, Kaushalendra Nath Tripathi, Raja Bhattacharya, Budithi Sudarsi, Deven Parmar, Kevin Kansagra, Hardik Pathak
Journal: Metabolism open