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

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 ≥18 years 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 1.0 mg/day, rivoglitazone 1.5 mg/day, or pioglitazone 45 mg/day, for 26 weeks. Results A total of 1912 subjects received placebo (n = 137), rivoglitazone 1.0 mg (n = 274), rivoglitazone 1.5 mg (n = 750) or pioglitazone (n = 751). Rivoglitazone 1.5 mg was statistically superior (p = 0.0339) and rivoglitazone 1.0 mg 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 1.5 mg was associated with statistically superior glycaemic control to pioglitazone 45 mg, while rivoglitazone 1.0 mg was non‐inferior; the safety profiles of the two drugs appeared similar.