Triple Fixed-dose combination of Dapagliflozin, Sitagliptin, and Metformin for People with Type 2 Diabetes in Indian Settings

Objective: This study assessed the bioequivalence of a fixed-dose combination (FDC) therapy containing extended-release Metformin (Metformin XR), Dapagliflozin, and Sitagliptin for treating type 2 diabetes (T2D). The objective was to compare the absorption rate and extent of the FDC with two reference products: Sitagliptin 100mg tablets (R1) and a combination of Dapagliflozin 10mg plus Metformin 1000mg extended-release tablets (R2) in healthy adult males under fed conditions. Methods: An open-label, randomized, cross-over study was conducted with 24 healthy male participants. Each participant received a single dose of the test FDC and the reference products, with blood samples collected over 72 hours to evaluate pharmacokinetic parameters (Cmax, AUC0-t, AUC0-inf, Tmax, Kel, AUC_% Extrap_obs, and t1/2). Bioequivalence was determined based on the 90% confidence intervals (CIs) of the geometric mean ratios for AUC0-t and Cmax, within a predefined range of 80.00%-125.00%. Safety and tolerability were also assessed. Results: Pharmacokinetic analysis was performed on 22 subjects. The geometric mean ratios for the FDC compared to the reference products were within the predefined bioequivalence range, indicating that the absorption profiles of the FDC and the reference products were similar. The mean plasma concentration-time curves for Dapagliflozin, Sitagliptin, and Metformin XR were almost identical between the FDC and reference products, demonstrating consistent drug release and absorption. No significant differences were observed in Tmax, t1/2, or other pharmacokinetic parameters, further supporting bioequivalence. Additionally, the FDC was well-tolerated, with no serious adverse events reported, and all subjects completed the study without complications. Conclusion: The study confirmed that the FDC of Dapagliflozin, Sitagliptin, and Metformin XR is bioequivalent to the reference products in healthy adult males under fed conditions. This bioequivalence supports the use of the FDC as an effective treatment option to improve glycemic control in adults with T2D, particularly in the Indian context, promoting the benefits of combined therapy in managing diabetes. Keywords: Bioequivalence, Fixed-dose combination (FDC), Type 2 diabetes (T2D), Pharmacokinetics, Dapagliflozin, Metformin XR, Sitagliptin