Evaluation of the Bioequivalence of two Linagliptin/Metformin Hydrochloride 2.5/1000 mg Fixed-Dose Combination Tablets in Healthy Adults Under Fed Conditions: A Study from Bangladesh

Author(s): Sabrina Akter Tushi, Md. Ashiqur Rahman, Uttom Kumar Bhowmik, Nayan Ghosh, Nithon Chandra Sahana, Md. Ashraful Islam, Md. Alimur Reza

Background: Fixed-dose combinations (FDCs) of linagliptin and metformin hydrochloride are commonly used in the treatment of type 2 diabetes mellitus (T2DM) due to their complementary mechanisms of action. Establishing bioequivalence between a generic formulation and an innovator product is essential to ensure comparable safety and efficacy.

Aims: To evaluate the bioequivalence of a test formulation of linagliptin and metformin hydrochloride 2.5/1000 mg tablets with the reference product, Trajentamet®, under fed conditions in healthy adult Bangladeshi subjects.

Methods: In this randomized, open-label, two-period, two-sequence, crossover study, healthy volunteers received a single dose of the test or reference product under fed conditions, with a 7-day washout period between doses. Plasma concentrations of linagliptin and metformin were determined using validated LC-MS/MS methods. Pharmacokinetic parameters, including Cmax, AUC0-t, and AUC0-∞, were calculated. Bioequivalence was assessed using 90% confidence intervals (CIs) for the test-to-reference (T/R) geometric mean ratios, with acceptance criteria of 80%–125%. Statistical analysis was performed using SAS® software, calculating the ratios of least square means and confidence intervals for primary pharmacokinetic parameters.

Results: A total of 24 healthy male subjects (mean age 24.09 ± 3.26 years) completed the study. The T/R ratio of Least Squares Geometric Means and 90% confidence intervals for log-transformed data for Cmax and AUC measures of Linagliptin and Metformin were within the bioequivalence range of 80%–125%. For Linagliptin, Cmax was 103.55% and AUC0-72 was 103.81%. For Metformin, Cmax was 98.99%, AUC0-t was 100.45% and AUC0-∞ was 100.19%, all within the bioequivalence range of 80%–125% for log-transformed values. Statistical analysis (ANOVA) confirmed no significant differences between the formulations, supporting bioequivalence for both drugs.

Conclusion: The test formulation of linagliptin and metformin hydrochloride 2.5/1000 mg tablets is bioequivalent to Trajentamet® under fed conditions in healthy Bangladeshi adults. These findings support its use as a safe and effective alternative in the management of T2DM.