A 26-week, placebo- and pioglitazone-controlled, dose-ranging study of rivoglitazone, a novel thiazolidinedione for the treatment of type 2 diabetes

OBJECTIVE: To examine the efficacy and general safety of rivoglitazone, a novel thiazolidinedione, as a treatment for type 2 diabetes in a dose-ranging study over a period of up to 6 months. RESEARCH DESIGN AND METHODS: A 26-week, randomized, double-blind, double-dummy, placebo- and active comparator (pioglitazone 45 mg)-controlled study designed to evaluate the efficacy and safety of once-daily rivoglitazone 1, 2, or 3 mg in subjects with type 2 diabetes. The study was conducted in adults with type 2 diabetes (glycated hemoglobin HbA(1c) >or=7.0% and 50%, with most cases being related to a lack of efficacy (highest on placebo) or adverse experiences (highest on rivoglitazone 3 mg). Rivoglitazone 1, 2, and 3 mg and pioglitazone 45 mg were more effective than placebo in reducing HbA(1c) from baseline to week 26 (placebo-subtracted change from baseline: -0.55% p = 0.0034, -0.99% p < 0.0001, -1.10% p < 0.0001, and -0.59% p = 0.0016, respectively). In general, all treatments were safe. The most common drug-related adverse events reported with rivoglitazone were peripheral edema and weight gain; incidences increased with dose and were higher with rivoglitazone 2 and 3 mg than with pioglitazone or rivoglitazone 1 mg. CONCLUSIONS: Rivoglitazone is a potent thiazolidinedione agent with demonstrated glycemic benefits over a 6-month period in subjects with type 2 diabetes. Once-daily doses of 1, 2, and 3 mg rivoglitazone demonstrated HbA(1c) reduction similar or superior to those observed for pioglitazone 45 mg. Limitations in generalizing from this study include a modest sample size and a high rate of discontinuation prior to the last scheduled visit.