Kohei Kaku1. 1. Diabetes and Endocrine Division, Department of Medicine, Kawasaki Medical School, Okayama, Japan. kka@med.kawasaki-m.ac.jp
Abstract
OBJECTIVE: To assess the efficacy and safety of combination therapy with pioglitazone and metformin in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: During 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. RESULTS:Mean 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%). CONCLUSION:Pioglitazone 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 NUMBER: UMIN 000001110.
RCT Entities:
OBJECTIVE: To assess the efficacy and safety of combination therapy with pioglitazone and metformin in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: During 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. RESULTS: Mean 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%). CONCLUSION:Pioglitazone 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 NUMBER: UMIN 000001110.
Authors: A Avogaro; M Federici; J Betteridge; R Bonadonna; I W Campbell; G H Schernthaner; B Staels; E Farinaro; G Crepaldi Journal: J Endocrinol Invest Date: 2011-11 Impact factor: 4.256
Authors: Dennis Schrijnders; Raiza Wever; Nanne Kleefstra; Sebastiaan T Houweling; Kornelis J J van Hateren; Geertruida H de Bock; Henk J G Bilo; Klaas H Groenier; Gijs W D Landman Journal: Diabetes Obes Metab Date: 2016-07-13 Impact factor: 6.577