Bioequivalence of a Metformin/Linagliptin Fixed-Dose Combination Tablet Compared With Coadministered Single Extended-Release Agents in Healthy Adult Subjects

Abstract

Aim: We aimed to demonstrate the bioequivalence of a fixed-dose combination (FDC) tablet of metformin 1000 mg and linagliptin 5 mg compared with the coadministration of their respective extended-release (XR) single tablets in healthy Korean adults under fasting conditions.

Methods: This randomized, open-label, 2-sequence, 2-period crossover study included 64 healthy Korean adults. The participants received a single dose of the FDC tablet or the individual XR tablets of metformin and linagliptin, with a 49 days washout period between treatments. Blood samples were collected over a 72-h period to measure the pharmacokinetic parameters, including area under the curve (AUC) and maximum concentration (C_max). The safety and tolerability were also assessed.

Results: Our pharmacokinetic analysis showed that the AUC and C_max for both metformin and linagliptin in the FDC tablet were within the bioequivalence range of 80%–125% compared with those of the individual XR tablets. Specifically, the geometric mean ratios (FDC to coadministration) for metformin were 101.1% (95% confidence interval (CI): 97.8–104.5) for AUC and 97.6% (95% CI: 94.5–100.9) for C_max and those for linagliptin were 98.4% (95% CI: 95.7–101.2) for AUC and 96.7% (95% CI: 93.9–99.5) for C_max. No serious adverse events (AEs) were reported, and both treatments were well tolerated.

Conclusion: The metformin/linagliptin 1000 mg/5 mg FDC tablet is bioequivalent to coadministration of individual XR tablets in healthy Korean adults under fasting conditions. The FDC tablet was well tolerated, indicating that it is a safe and effective option that could improve medication adherence and treatment outcomes in patients with type 2 diabetes.