Muraglitazar, a dual (α/γ) PPAR activator: A randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with type 2 diabetes

• Published in: Clinical therapeutics 2005-08, Vol.27 (8), p.1181-1195
• Main Authors: Buse, John B., Rubin, Cindy J., Frederich, Robert, Viraswami-Appanna, Kalyanee, Lin, Kwo-Chuan, Montoro, Rafael, Shockey, Gerald, Davidson, Jaime A.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Atherosclerosis; Biological and medical sciences; Blood Glucose; Cardiovascular disease; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Double-Blind Method; Drug dosages; dual (α/γ) PPAR activator; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epidemiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fasting - metabolism; Fatty acids; Female; Glucose; Glycated Hemoglobin A - drug effects; Glycine - analogs & derivatives; Glycine - therapeutic use; Humans; Hypoglycemic Agents - therapeutic use; Insulin - blood; Insulin resistance; Lipids; Lipoproteins; Male; Medical sciences; Metabolic disorders; Middle Aged; oral antidiabetic therapy; Oxazoles - therapeutic use; Peroxisome Proliferator-Activated Receptors - agonists; Pharmacology. Drug treatments; PPAR agonist; treatment option; type 2 diabetes
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2005.08.005

Abstract Peroxisome proliferator-activated receptors (PPARs) present a therapeutic target, and simultaneous activation of PPAR-α and PPAR-γ may provide improvements in glycemic control and dyslipidemia in patients with type 2 diabetes. The goal of this study was to evaluate the efficacy and safety of muraglitazar, a dual (α/γ) PPAR activator, in adult patients with type 2 diabetes whose disease was inadequately controlled by diet and exercise. This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter, 24-week monotherapy study in drug-naive, type 2 diabetes patients with inadequate glycemic control. Men and women aged 18 to 70 years with a body mass index ≤41 kg/m 2 and serum triglyceride levels ≤600 mg/dL were eligible for study participation. The study included double-blind and open-label treatment phases. Patients with glycosylated hemoglobin (HbA 1c) levels ≥7.0% and ≤10.0% at screening were enrolled in the double-blind treatment phase. These patients received treatment with muraglitazar 2.5 mg, muraglitazar 5 mg, or placebo. Patients with HbA 1c levels >10.0% and ≤12.0% who met all other study criteria were eligible for enrollment in a 24-week, open-label evaluation of muraglitazar 5 mg. The primary end point was the mean change from baseline in HbA 1c levels after 24 weeks of treatment. A total of 340 patients (179 men, 161 women) participated in the double-blind treatment phase of the study. Patients had mean baseline HbA 1c levels of 7.9% to 8.0%. Monotherapy with muraglitazar 2.5 and 5 mg significantly reduced HbA 1c levels (−1.05% and −1.23%, respectively) compared with placebo (−0.32%; P < 0.001). At week 24, 58%, 72%, and 30% of the patients receiving muraglitazar 2.5 mg, muraglitazar 5 mg, and placebo, respectively, achieved the American Diabetes Association-recommended HbA 1c goal of