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DOI: 10.2337/dc05-1146
© 2006 by the American Diabetes Association
Emerging Treatments and Technologies |
Improvement of Glycemic Control, Triglycerides, and HDL Cholesterol Levels With Muraglitazar, a Dual (
/
) Peroxisome Proliferator–Activated Receptor Activator, in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy
A double-blind, randomized, pioglitazone-comparative study
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
OBJECTIVE—We sought to evaluate the effects of muraglitazar, a dual (
/
) 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 HbA1c (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 pioglitazone reduced mean plasma triglyceride (–28 vs. –14%), apolipoprotein B (–12 vs. –6%), and non-HDL cholesterol (–6 vs. –1%) and increased HDL cholesterol (19 vs. 14%), respectively (P < 0.0001 vs. pioglitazone for all comparisons). At week 24, weight gain (1.4 and 0.6 kg, respectively) and edema (9.2 and 7.2%, respectively) were observed in the muraglitazar and pioglitazone groups; at week 50, weight gain and edema were 2.5 and 1.5 kg, respectively, and 11.8 and 8.9%, respectively. At week 50, heart failure was reported in seven patients (five with muraglitazar and two with pioglitazone), and seven deaths occurred: three from sudden death, two from cerebrovascular accident, and one from pancreatic cancer in the muraglitazar group and one from perforated duodenal ulcer in the pioglitazone group.
CONCLUSIONS—We found that 5 mg muraglitazar resulted in greater improvements in A1C and lipid parameters than a submaximal dose of 30 mg pioglitazone when added to metformin. Weight gain and edema were more common when muraglitazar was compared with a submaximal dose of pioglitazone.
Abbreviations: apo, apolipoprotein • CHF, congestive heart failure • CRP, C-reactive protein • CVD, cardiovascular disease • FFA, free fatty acid • FPG, fasting plasma glucose • HOMA-IR, homeostasis model assessment of insulin resistance • LOCF, last observation carried forward • NYHA, New York Heart Association • PAI-1, plasminogen activator inhibitor type 1 • PPAR, peroxisome proliferator–activated receptor
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