| Sumario: | What is known and objective Both metformin and acarbose are recommended monotherapy and add-on therapy in type 2 diabetes mellitus ( T2 DM). A fixed-dose combination ( FDC) of acarbose and metformin has been developed to reduce pill burden and potentially improve compliance. The current study investigated the bioequivalence of the acarbose/metformin FDC compared with the individual agents administered simultaneously (loose combination). Secondary endpoints were the safety and tolerability of the FDC and the potential for drug-drug interactions between acarbose and metformin. Methods A single-centre, randomized, open-label, four-period crossover study was conducted in healthy male Korean subjects aged 18-45 years. Following one-period balanced Williams design, participants were randomized to receive four single oral treatments on different study days separated by ≥7 days' washout. Treatments were as follows: (i) acarbose/metformin 50/500 mg FDC (test); (ii) acarbose 50 mg and metformin 500 mg as loose combination (reference); (iii) acarbose 50 mg; and (iv) metformin 500 mg. Serial blood samples were taken for glucose and insulin levels for 4 h after a sucrose load on the day before and day of study drug administration. Additionally, serial blood samples were taken for analysis of metformin levels for 24 h after each drug containing metformin. The area under the curve for 4 h post-test ( AUC0-4 h) and the maximal serum concentration ( Cmax) of plasma glucose and serum insulin were primary pharmacodynamic ( PD) parameters, and Cmax, AUC0-last and AUC for metformin levels were primary pharmacokinetic ( PK) parameters. The bioequivalence of the FDC to the loose combination was considered established if the 90% confidence intervals ( CIs) of the baseline-adjusted PD parameter ratios (test vs. reference) for plasma glucose and the PK parameter ratios for metformin fell completely within current acceptance limits (0·8-1·25). Results and discussion Thirty-three of 40 randomized subjects completed the study; five withdrew consent and two discontinued because of adverse events ( AEs). The 24-h plasma concentration-time curves of metformin and the 4-h plasma glucose-time curves after acarbose/metformin FDC (test) and acarbose + metformin loose combination (reference) were almost superimposable. The geometric least squares ( LS) mean of the Ratio AUC and
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