Improvement of glycemic control, triglycerides, and HDL cholesterol levels with muraglitazar, a dual (alpha/gamma) peroxisome proliferator-activated receptor activator, in patients with type 2 diabetes inadequately controlled with metformin monotherapy: A double-blind, randomized, pioglitazone-comparative study.

Abstract

OBJECTIVE:

We sought to evaluate the effects of muraglitazar, a dual (alpha/gamma) 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.

• Authors: David M Kendall, Cindy J Rubin, Pharis Mohideen, Jean-Marie Ledeine, Rene Belder, Jorge Gross, Paul Norwood, Michael O'Mahony, Kenneth Sall, Greg Sloan, Anthony Roberts, Fred T Fiedorek, Ralph A DeFronzo
• Journal: Diabetes care (Diabetes Care) Vol. 29 Issue 5 Pg. 1016-23 (May 2006) ISSN: 0149-5992 [Print] United States
• PMID: 16644631 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Cholesterol, HDL
• Hypoglycemic Agents
• Oxazoles
• PPAR alpha
• PPAR gamma
• Thiazolidinediones
• Triglycerides
• Metformin
• Glycine
• muraglitazar
• Pioglitazone

Topics

• Adult
• Blood Glucose (metabolism)
• Cholesterol, HDL (blood)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Double-Blind Method
• Female
• Glycine (adverse effects, analogs & derivatives, therapeutic use)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Male
• Metformin (therapeutic use)
• Middle Aged
• Oxazoles (adverse effects, therapeutic use)
• PPAR alpha (agonists)
• PPAR gamma (agonists)
• Pioglitazone
• Thiazolidinediones (adverse effects, therapeutic use)
• Triglycerides (blood)