A 26-week, placebo- and pioglitazone-controlled monotherapy study of rivoglitazone in subjects with type 2 diabetes mellitus

Abstract

Aims: To evaluate the efficacy and safety of rivoglitazone, a peroxisome proliferator-activated receptor γ agonist in the thiazolidinedione class, in subjects with suboptimally controlled type 2 diabetes mellitus (T2DM). Methods: Subjects aged ≥18years with T2DM and haemoglobin A1c (HbA1c) >7.0% and ≤8.5%, who were treatment naïve or receiving a non-thiazolidinedione antidiabetes monotherapy, entered a 2-week washout and single-blind placebo run-in period and were then randomized 2:4:11:11 to double-blind treatment with placebo, rivoglitazone 1.0mg/day, rivoglitazone 1.5mg/day, or pioglitazone 45mg/day, for 26weeks. Results: A total of 1912 subjects received placebo (n=137), rivoglitazone 1.0mg (n=274), rivoglitazone 1.5mg (n=750) or pioglitazone (n=751). Rivoglitazone 1.5mg was statistically superior (p=0.0339) and rivoglitazone 1.0mg was non-inferior (p=0.0339) to pioglitazone in reducing HbA1c from baseline (changes of -0.7%, -0.4% and -0.6%, respectively). Rivoglitazone also significantly reduced fasting plasma glucose from baseline (p<0.0001). Rivoglitazone significantly improved estimates of insulin sensitivity, high-density lipoprotein cholesterol levels, and other metabolic and inflammatory biomarkers. Rivoglitazone was generally well tolerated at both doses, with treatment-emergent adverse event (TEAE) rates similar to pioglitazone. The most common drug-related TEAEs were peripheral oedema (active, 5.2-6.2%; placebo 0.7%), increased weight (active, 1.6-3.1%; placebo, 0%) and pitting oedema (active, 1.3-2.2%; placebo, 0%). Conclusions: In subjects with suboptimally controlled T2DM, rivoglitazone 1.5mg was associated with statistically superior glycaemic control to pioglitazone 45mg, while rivoglitazone 1.0mg was non-inferior; the safety profiles of the two drugs appeared similar. © 2012 Blackwell Publishing Ltd.