Bioequivalence Evaluation of Two Metformin/Empagliflozin Fixed‐Dose Combination Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions: A Randomized, Open‐Label, Crossover Study

This study evaluated the bioequivalence and safety of two fixed‐dose combination (FDC) tablet formulations of metformin/empagliflozin (1000 mg/5 mg) in healthy Chinese subjects. A single‐center, open‐label, randomized, two‐period, two‐treatment, and two‐sequence crossover study was conducted, enrolling 56 subjects who were assigned to either fasting or fed conditions in a 1:1 ratio. Each subject received both the test and reference formulations, with a 7‐day washout period between administrations. Blood samples were collected up to 48 h post‐dose, and plasma concentrations of metformin and empagliflozin were determined using a validated liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) method. Bioequivalence was assessed based on key pharmacokinetic parameters—C max , AUC 0–t , and AUC 0–∞ —with the geometric least‐squares mean ratios of the test to reference formulation falling within the accepted bioequivalence range of 80.00% to 125.00% for all 90% confidence intervals under both fasting and fed states. High‐fat meals significantly reduced the C max of metformin and empagliflozin by approximately 47% and 28%, respectively, and their overall exposure (AUC 0−∞ ) by approximately 29% and 15%, respectively. No serious adverse events were reported. In conclusion, the test and reference formulations of metformin/empagliflozin FDC tablets were bioequivalent and well‐tolerated under both fasting and fed conditions.