A Randomized, Multicenter Study Evaluating the Efficacy, Safety and Tolerability of Dapagliflozin + Gliclazide Fixed Dose Combination Over Dapagliflozin Monotherapy in Type 2 Diabetes Mellitus Patients Inadequately Controlled on Metformin Monotherapy

Background Sodium glucose transporter 2 inhibitors (SGLT2i) and sulfonylurea (SU) offer an additive mechanism of action, potentially enhancing glycemic control in patients inadequately managed with metformin monotherapy. This study compared the efficacy and safety of a fixed-dose combination (FDC) of dapagliflozin and gliclazide sustained release (SR) in patients with type 2 diabetes mellitus (T2DM) poorly controlled with metformin monotherapy. Methods This multicentric, prospective, randomized, open-label, parallel-group, phase III clinical study was carried out at several sites around India. A total of 244 T2DM patients were randomized in a 1:1 ratio to receive either dapagliflozin 10 mg + gliclazide 60 mg SR (test arm) or dapagliflozin 10 mg (reference arm) for 16 weeks. The primary endpoint was the adjusted mean change from baseline in glycated hemoglobin A1c (HbA1c) at the end of week 16. Results In both arms, the baseline mean HbA1c was 8%. From baseline to week 16, the adjusted mean reduction in HbA1c was statistically significant in the FDC combination of dapagliflozin and gliclazide SR compared to dapagliflozin, with a change in mean HbA1c levels from baseline of 8.76% to 6.97% (SD: 1.02%; p-value < 0.001) and 8.80% to 7.32% (SD: 1.24%; p-value < 0.001), respectively. The FDC was well-tolerated with a favorable safety profile. Conclusion The FDC of dapagliflozin 10 mg and gliclazide 60 mg SR proved to be efficacious and exhibited a favorable safety profile in patients with T2DM poorly controlled with metformin compared to dapagliflozin 10 mg monotherapy.