Bioequivalence of Dapagliflozin, Glimepiride, and Metformin FDC in Healthy Indian Volunteers

Objectives: A fixed-dose combination (FDC) of Dapagliflozin, Glimepiride, and Metformin Extended-Release (ER) offers a comprehensive strategy for Type 2 diabetes (T2D), focusing on glycaemic control, reduction of cardiovascular (CV) risk, and improved adherence through decreased pill burden. This study aimed to assess the bioequivalence and safety of this FDC in healthy Indian adult volunteers under fed conditions. Methods: This was a randomised, open-label, two-treatment, two-period, two-sequence, single-dose, crossover bioequivalence study. Twenty-four healthy adult male subjects received either the test FDC tablet (Dapagliflozin 10 mg/Glimepiride 2 mg/Metformin ER 1000 mg) or the reference formulations—Oxramet® XR (Dapagliflozin 10 mg/Metformin ER 1000 mg) plus Amaryl® 2 mg (Glimepiride)—with a 7-day washout period. Plasma concentrations were measured up to 48 hours post-dose using LC-MS/MS, and pharmacokinetic parameters were calculated. Bioequivalence was concluded if the 90% confidence intervals (CIs) for Cmax, AUC₀–t, and AUC₀–∞ were within the 80– 125% range. Results: All subjects completed the study. The plasma concentration-time curves of the test and reference products were nearly superimposable. The 90% CIs for all three analytes fell within the bioequivalence range of –125%. No serious adverse events were reported, and both formulations were well tolerated. Conclusion: The Dapagliflozin/Glimepiride/Metformin ER FDC is bioequivalent to the reference products and welltolerated under fed conditions. This FDC may serve as a simplified and effective therapeutic option for management in clinical practice.