• Kohei Kaku.
• Diabetes and Endocrine Division, Department of Medicine, Kawasaki Medical School, Okayama, Japan. kka@med.kawasaki-m.ac.jp
• Curr Med Res Opin. 2009 May 1; 25 (5): 111111191111-9.

ObjectiveTo assess the efficacy and safety of combination therapy with pioglitazone and metformin in Japanese patients with type 2 diabetes.Research Design And MethodsDuring a 12-week observation period 236 patients were treated with metformin 500 or 750 mg/day. 169 patients with a confirmed HbA(1c) level >or= 6.5% were randomized (stratified according to metformin dosage) to receive pioglitazone 15 mg/day for 12 weeks then increased to 30 mg/day for a further 16 weeks (n = 83), or placebo (n = 86). Outcome measures included HbA(1c), fasting blood glucose (FBG), percentage of patients achieving HbA(1c) < 6.5%, lipid profile, and other metabolic parameters.ResultsMean HbA(1c) was reduced by 0.67% in patients receiving pioglitazone plus metformin versus an increase of 0.25% in those receiving metformin alone (p < 0.0001). After 8 weeks' treatment and until the end of the study, HbA(1c) was significantly lower with pioglitazone plus metformin and more patients in this group achieved an HbA(1c) < 6.5% (38.6% vs. 8.1%; p < 0.0001). FBG was also reduced by a significantly greater amount in patients receiving pioglitazone plus metformin compared with metformin monotherapy (-20.5 vs. 1.9 mg/dl; p < 0.0001). Combination therapy was associated with significantly increased HDL-cholesterol, total cholesterol, and adiponectin, and significantly decreased levels of fasting insulin, free fatty acids, and homeostasis model assessment insulin resistance (HOMA-R) compared with metformin monotherapy. Overall, combination therapy and monotherapy were equally well tolerated and the incidence of adverse effects 'possibly' related to therapy was 15.7% and 11.6% (p = 0.505), respectively. Edema occurred slightly more often in the combination group (6.0 vs. 1.2%).ConclusionPioglitazone plus metformin significantly improved glycemic control (HbA(1c) and FBG), and markers associated with increased insulin resistance and cardiovascular risk compared with metformin monotherapy.Clinical Trial Registration NumberUMIN 000001110.

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