A 26-week, placebo- and pioglitazone-controlled monotherapy study of rivoglitazone in subjects with type 2 diabetes mellitus.
OBJECTIVE
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.
Daiichi Sankyo Pharma Development, Edison, NJ 08837, USA. hchou@dsi.com
H S
HS
Chou
K E
KE
Truitt
J B
JB
Moberly
D
D
Merante
Y
Y
Choi
Y
Y
Mun
A
A
Pfützner
D054316:Biomarkers, Pharmacological; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007194:India / Q000453:epidemiology; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D016037:Single-Blind Method; D013019:South Africa / Q000453:epidemiology; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D054316:Biomarkers, Pharmacological; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077205:Pioglitazone; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human; C521549:rivoglitazone