HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kendall, D. M. Articles by DeFronzo, R. A. Search for Related Content PubMed PubMed Citation Articles by Kendall, D. M. Articles by DeFronzo, R. A. Social Bookmarking                What's this?

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 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 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

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				F. Biscetti, E. Gaetani, A. Flex, T. Aprahamian, T. Hopkins, G. Straface, G. Pecorini, E. Stigliano, R. C. Smith, F. Angelini, et al. Selective Activation of Peroxisome Proliferator-Activated Receptor (PPAR){alpha} and PPAR{gamma} Induces Neoangiogenesis Through a Vascular Endothelial Growth Factor-Dependent Mechanism Diabetes, May 1, 2008; 57(5): 1394 - 1404. [Abstract] [Full Text] [PDF]

				C. Schindler Review: The metabolic syndrome as an endocrine disease: is there an effective pharmacotherapeutic strategy optimally targeting the pathogenesis? Therapeutic Advances in Cardiovascular Disease, October 1, 2007; 1(1): 7 - 26. [Abstract] [PDF]

				F. Chang, L. A Jaber, H. D Berlie, and M. B. O'Connell Evolution of Peroxisome Proliferator-Activated Receptor Agonists Ann. Pharmacother., June 1, 2007; 41(6): 973 - 983. [Abstract] [Full Text] [PDF]

				J. Karalliedde and G.C. Viberti Comment on: Boden et al. (2007) Combined Use of Rosiglitazone and Fenofibrate in Patients with Type 2 Diabetes: Prevention of Fluid Retention: Diabetes 56:248-255 Diabetes, May 1, 2007; 56(5): e3 - e3. [Full Text] [PDF]

				E. Tozzo, R. Ponticiello, J. Swartz, D. Farrelly, R. Zebo, G. Welzel, D. Egan, L. Kunselman, A. Peters, L. Gu, et al. The Dual Peroxisome Proliferator-Activated Receptor {alpha}/{gamma} Activator Muraglitazar Prevents the Natural Progression of Diabetes in db/db Mice J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 107 - 115. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Prevention of Cardiovascular Disease Diabetes Care, February 1, 2007; 30(2): 423 - 431. [Abstract] [Full Text] [PDF]

				D. Zhang, L. Wang, G. Chandrasena, L. Ma, M. Zhu, H. Zhang, C. D. Davis, and W. G. Humphreys Involvement of Multiple Cytochrome P450 and UDP-Glucuronosyltransferase Enzymes in the in Vitro Metabolism of Muraglitazar Drug Metab. Dispos., January 1, 2007; 35(1): 139 - 149. [Abstract] [Full Text] [PDF]

				D. Zhang, L. Wang, N. Raghavan, H. Zhang, W. Li, P. T. Cheng, M. Yao, L. Zhang, M. Zhu, S. Bonacorsi, et al. Comparative Metabolism of Radiolabeled Muraglitazar in Animals and Humans by Quantitative and Qualitative Metabolite Profiling Drug Metab. Dispos., January 1, 2007; 35(1): 150 - 167. [Abstract] [Full Text] [PDF]

				D. Conlon Goodbye glitazars? The British Journal of Diabetes & Vascular Disease, May 1, 2006; 6(3): 135 - 137. [Abstract] [PDF]