Pharmacokinetic comparison of sitagliptin and metformin HCl extended-release tablets versus JANUMET® XR in healthy volunteers under fasting and fed conditions.

Abstract

Background and Objectives: Janumet® XR is the combination of sitagliptin and extended metformin hydrochloride produced by Merck Sharp & Dohme. It is specially designed for diabetes mellitus patients taking both drugs already. Janumet® XR exhibited clinically significant blood glucose lowering efficacy and long-term use safety. However, no generic form of Janumet® XR has been approved in western countries. The relatively high cost made the medication less prescribed. A more affordable form of this drug may benefit an immense diabetes mellitus population. The current study compared the bioequivalence (BE) of sitagliptin 100mg and metformin 1000mg produced by Nanjing Chia-Tai Tianqing Pharmaceutical Company to Janumet® XR in healthy Chinese subjects. Methods: Twenty-eight healthy Chinese subjects were enrolled in Study 1 and 2, respectively. Both studies were conducted with an open, randomized, two-period crossover design using the test (T) or the reference (R) drug. Study 1 is conducted under the fasting state, and Study 2 is under the fed state. Subjects received an oral dose of sitagliptin 100mg and metformin 1000mg, and plasma concentrations of sitagliptin and metformin were determined up to 72h post-dose. Pharmacokinetic (PK) parameters, including maximum serum concentration (Cmax) and area under the concentration-time curve up to the last quantifiable concentration (AUC0-t) of both sitagliptin and metformin, were calculated and compared between the T and R treatments. Results: In the fasting study, the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ for sitagliptin were 109.42%, 101.93%, and 101.95%, respectively; the corresponding ratios for metformin were 98.69%, 94.12%, and 93.42%, respectively. In the fed study, the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ for sitagliptin were 98.41%, 100.30%, and 100.24%, respectively; the corresponding ratios for metformin were 97.79%, 99.28%, and 100.69%, respectively. The 90% CIs of Cmax, AUC0-t, and AUC0-∞ in both studies were all within acceptance limits (80.00%-125.00%). Conclusion: The results demonstrated for the first time that sitagliptin 100mg and metformin 1000mg produced by Nanjing Chia-Tai Tianqing Pharmaceutical Company was bioequivalent to the branded Janumet® XR, and both drugs were well tolerated.