Bioequivalence study of two formulations of a sitagliptin/metformin hydrochloride extended-release tablet in healthy Chinese subjects under fasting and fed conditions: a randomized, open-label, single-dose, crossover trial

Introduction This study aimed to evaluate the bioequivalence and safety of a newly developed generic sitagliptin/metformin hydrochloride extended‐release (XR) tablet (50 mg/500 mg) compared with the reference formulation, Janumet XR, in healthy Chinese subjects under fasting and fed conditions. Methods This randomized, open‐label, single‐dose, two‐period, two‐sequence crossover study included 40 subjects in the fasting cohort and 36 subjects in the fed cohort. Subjects received a single dose of the test or reference formulation in each period, separated by a 5‐day washout period. Plasma concentrations of sitagliptin and metformin were determined using a validated liquid chromatography‐tandem mass spectrometry method. Bioequivalence was assessed using the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs; test/reference) of maximum plasma concentration (C max ), area under the plasma concentration‐time curve from time zero to the last quantifiable concentration (AUC 0‐t ), and area under the plasma concentration‐time curve from time zero to infinity (AUC 0‐infinity ). Results Under fasting conditions, the 90% CIs for the GMRs of sitagliptin for C max , AUC 0‐t , and AUC 0‐infinity were 88.24%–101.46%, 98.24%–103.15%, and 98.41%–103.33%, respectively. The corresponding values for metformin were 93.23%–103.26%, 93.00%–106.20%, and 92.89%–105.74%. Bioequivalence was also established under fed conditions for sitagliptin (C max : 88.29%–99.06%; AUC 0‐t : 96.19%–101.02%; AUC 0‐infinity : 96.07%–101.04%) and metformin (C max : 92.06% –99.39%; AUC 0‐t : 91.31%–100.06%; AUC 0‐infinity : 91.00%–99.30%). Analysis of variance showed a significant period effect for metformin AUC 0‐t and AUC 0‐infinity under fasting conditions (P < 0.05), whereas no significant formulation effect was observed (P > 0.05). Both formulations were well tolerated. Only Grade 1 or Grade 2 adverse events were reported, and no serious adverse events occurred Discussion The generic sitagliptin/metformin hydrochloride XR tablet was bioequivalent to the reference product under both fasting and fed conditions in healthy Chinese subjects. The generic formulation was well tolerated and may provide a safe and effective alternative for the treatment of type 2 diabetes mellitus.