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 <10.5%) who were either naïve to prior antidiabetes drug treatment or discontinued pre-study antidiabetes medications and were switched to study medication. A total of 441 subjects were randomized, using an equal allocation schedule to one of five treatment arms, including placebo. The primary efficacy measurement was the change in HbA(1c) from baseline to week 26 in the intent-to-treat population (last observation carried forward), for drug treatments minus placebo (placebo-subtracted). CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00143520. RESULTS: The incidence of early discontinuations was >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.