Pioglitazone hydrochloride monotherapy improves glycemic control in the treatment of patients with type 2 diabetes - A 6-month randomized placebo-controlled dose-response study

OBJECTIVE - To evaluate the efficacy and safety of four doses of pioglitazo ne monotherapy in the treatment of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - There were 408 patients randomized in this mu lticenter double-blind placebo-controlled clinical trial. Patients who had HbA(1c) greater than or equal to7.0%, fasting plasma glucose (FPG) greater than or equal to 140 mg/dl, and C-peptide >1 ng/ml were randomized to recei ve placebo or 7.5, 15, 30, or 45 mg pioglitazone administered once a day fo r 26 weeks. RESULTS - Patients treated with 15, 30, or 45 mg pioglitazone had significa nt mean decreases in HbA(1c) (range -1.00 to -1.60% difference from placebo ) and FPG (-39.1 to -65.3 mg/dl difference from placebo). The decreases in FPG were observed as early as the second week of therapy; maximal decreases occurred after 10-14 weeks and were maintained until the end of therapy (w eek 26). In the 15-, 30-, or 45-mg pioglitazone groups, there were signific ant mean percent decreases in triglycerides, significant mean percent incre ases in HDL cholesterol, and only small percent changes in total cholestero l and LDL. The subset of patients naive to therapy had greater improvements in HbA(1c) and FPG (difference from placebo of -2.55% and -79.9 mg/dl for the 45-mg group) compared with previously treated patients. The overall adv erse event profile of pioglitazone was similar to that of placebo. There wa s no evidence of drug-induced hepatotoxicity or drug-induced elevations of alanine aminotransferase levels in this study. CONCLUSIONS - Pioglitazone monotherapy significantly improves HbA(1c) and F PG while producing beneficial effects on serum lipids in patients with type 2 diabetes with no evidence of drug-induced hepatotoxicity.