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Evaluation of the bioequivalence of a fixed-dose combination tablet of pioglitazone-metformin versus commercial tablets in healthy Japanese male volunteers

Shinzo Hiroi, Kumi Matsuno, Masashi Hirayama, Takaki Hayakawa,Norihito Yoshioka & Koji Kawakami

In chronic asymptomatic diseases such as Type 2 diabetes mellitus (T2DM) poor adherence to therapy is a common problem. Simplification of treatment regimens using fixed-dose combination formulations has the potential to improve patient compliance. In this randomized, crossover, single-dose study we evaluated the bioequivalence of a new fixed-dose combination of pioglitazone–metformin (30/500 mg) and commercial tablets (pioglitazone 30 mg plus metformin 2 × 250 mg) in 84 healthy Japanese male volunteers in a fasted state. The plasma concentration–time curves for unchanged pioglitazone and unchanged metformin were almost identical for the two formulations. The 90% confidence intervals for the ratios of maximum observed concentration (Cmax) and area under the plasma concentration–time curve from time 0 to 72 h (AUC0–72) for unchanged pioglitazone, and for Cmax and AUC0–48 of unchanged metformin, were within the 0.80–1.25 range, which meets the criterion for test-to-reference bioequivalence between the two formulations. In conclusion, the fixed-dose combination of pioglitazone–metformin was bioequivalent to pioglitazone and metformin commercial tablets administered separately. This simplified regimen (one vs three tablets) may be clinically useful in patients with T2DM and should help improve patient compliance leading to better glycemic control and improved patient outcomes.