AIM: To evaluate the efficacy and safety of a triple fixed-dose combination (FDC) therapy of dapagliflozin + glimepiride + metformin hydrochloride extended-release (DAPA + GLIM + MET ER) tablets in Indian patients with type 2 diabetes mellitus (T2DM) inadequately controlled by combination of GLIM + MET. MATERIALS AND METHODS: A phase III, randomized, open-label, active-controlled study was conducted for a maximum 30 weeks (primary treatment [16 weeks]
uptitration [12 weeks] and follow-up [2 weeks]). Eligible patients were randomized in a 1:1 ratio to receive either the FDC of DAPA + GLIM + MET ER or the FDC of GLIM + MET prolonged-release (PR) once-daily. The primary efficacy endpoint was a change in glycated haemoglobin (HbA1c) from baseline to week 16. RESULTS: The mean reduction in HbA1c from baseline to week 16 was significantly greater with the FDC of DAPA + GLIM + MET ER compared to the FDC of GLIM + MET PR (-1.98% ± 1.01% vs. -1.64% ± 0.86%, p = 0.0047). The mean reduction in HbA1c from baseline to week 12 was significantly greater with the FDC of DAPA + GLIM + MET ER versus dual FDC (p <
0.0001). The proportion of patients achieving HbA1c <
7.0% was significantly greater with the FDC of DAPA + GLIM + MET ER versus dual FDC at week 12 (19.1% vs. 6.5%
p = 0.0002) and week 16 (52.6% vs. 36.7%
p = 0.0015). A significant decrease in HbA1c, fasting and post-prandial blood glucose from baseline to weeks 12, 16, and 28 was observed in both arms. The incidence of TEAEs was similar across both arms. CONCLUSION: This study demonstrated that the FDC of DAPA + GLIM + MET ER tablets once daily was significantly better than dual FDC in achieving glycaemic control in patients with poorly controlled T2DM. Both treatments were well-tolerated. TRIAL REGISTRATION: CTRI/2022/03/041424, registered on 28 March 2022.