Improvement of Glycemic Control, Triglycerides, and HDL Cholesterol Levels With Muraglitazar, a Dual (α/γ) Peroxisome Proliferator–Activated Receptor Activator, in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy

Improvement of Glycemic Control, Triglycerides, and HDL Cholesterol Levels With Muraglitazar, a Dual (α/γ) Peroxisome Proliferator–Activated Receptor Activator, in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy A double-blind, randomized, pioglitazone-comparative study David M. Kendall , MD 1 , Cindy J. Rubin , MD 2 , Pharis Mohideen , MD 2 , Jean-Marie Ledeine , MSC 3 , Rene Belder , MD 2 , Jorge Gross , MD 4 , Paul Norwood , MD 5 , Michael O’Mahony , MD 6 , Kenneth Sall , MD 7 , Greg Sloan , MD 8 , Anthony Roberts , MBBS 9 , Fred T. Fiedorek , MD 2 and Ralph A. DeFronzo , MD 10 1 International Diabetes Center and the University of Minnesota, Minneapolis, Minnesota 2 Bristol-Myers Squibb, Princeton, New Jersey 3 Bristol-Myers Squibb, Braine-l’Alleud, Belgium 4 Centro De Pesquisa Em Diabetes, Rio Grande Do Sul, Brazil 5 Valley Research, Fresno, California 6 Corunna Medical Services, Ontario, Canada 7 Sall Research Medical Center, Bellflower, California 8 Emerald Coast Research Group, Chipley, Florida 9 South Australian Endocrine Clinical Research, Keswick Adelaide, Australia 10 University of Texas Health Sciences Center at San Antonio, San Antonio, Texas Address correspondence reprint requests to Ralph A. DeFronzo, MD, Department of Medicine, Division of Diabetes, University of Texas Health Sciences Center at San Antonio, Building HSC-DTL, Room 3.380S, 7703 Floyd Curl Dr., San Antonio, TX 78229. E-mail: albarado{at}uthscsa.edu Abstract OBJECTIVE —We sought to evaluate the effects of muraglitazar, a dual (α/γ) peroxisome proliferator–activated receptor (PPAR) activator within the new glitazar class, on hyperglycemia and lipid abnormalities. RESEARCH DESIGN AND METHODS —A double-blind, randomized, controlled trial was performed in 1,159 patients with type 2 diabetes inadequately controlled with metformin. Patients received once-daily doses of either 5 mg muraglitazar or 30 mg pioglitazone for a total of 24 weeks in addition to open-label metformin. Patients were continued in a double-blind fashion for an additional 26 weeks. RESULTS —Analyses were conducted at week 24 for HbA 1c (A1C) and at week 12 for lipid parameters. Mean A1C at baseline was 8.12 and 8.13% in muraglitazar and pioglitazone groups, respectively. At week 24, muraglitazar reduced mean A1C to 6.98% (−1.14% from baseline), and pioglitazone reduced mean A1C to 7.28% (−0.85% from baseline; P < 0.0001, muraglitazar vs. pioglitazone). At week 12, muraglitazar and