Metabolic effects of muraglitazar in type 2 diabetic subjects

M. Fernandez, A. Gastaldelli, C. Triplitt, J. Hardies, A. Casolaro, R. Petz, P. Tantiwong, N. Musi, E. Cersosimo, E. Ferrannini, Ralph A. DeFronzo

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Aim: To assess the effect of muraglitazar, a dual peroxisome proliferator-activated receptor (PPAR)γ-α agonist, versus placebo on metabolic parameters and body composition in subjects with type 2 diabetes mellitus (T2DM). Methods: Twenty-seven T2DM subjects received oral glucose tolerance test (OGTT), euglycaemic insulin clamp with deuterated glucose, measurement of total body fat (DEXA), quantitation of muscle/liver (MRS) and abdominal subcutaneous and visceral (MRI) fat, and then were randomized to receive, in addition to diet, muraglitazar (MURA), 5 mg/day, or placebo (PLAC) for 4 months. Results: HbA1cc decreased similarly (2.1%) during both MURA and PLAC treatments despite significant weight gain with MURA (+2.5 kg) and weight loss with PLAC (-0.7 kg). Plasma triglyceride, LDL cholesterol, free fatty acid (FFA), hsCRP levels all decreased with MURA while plasma adiponectin and HDL cholesterol increased (p < 0.05-0.001). Total body (muscle), hepatic and adipose tissue sensitivity to insulin and β cell function all improved with MURA (p < 0.05-0.01). Intramyocellular, hepatic and abdominal visceral fat content decreased, while total body and subcutaneous abdominal fat increased with MURA (p < 0.05-0.01). Conclusions: Muraglitazar (i) improves glycaemic control by enhancing insulin sensitivity and β cell function in T2DM subjects, (ii) improves multiple cardiovascular risk factors, (iii) reduces muscle, visceral and hepatic fat content in T2DM subjects. Despite similar reduction in A1c with PLAC/diet, insulin sensitivity and β cell function did not improve significantly.

Original languageEnglish (US)
Pages (from-to)893-902
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume13
Issue number10
DOIs
StatePublished - Oct 2011

Keywords

  • Insulin secretion
  • Insulin sensitivity
  • Muraglitazar
  • Muscle/liver/adipocyte
  • PPARα
  • PPARγ
  • Thiazolidinediones

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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