title: Metabolic effects of muraglitazar in type 2 diabetic subjects.
abstract: OBJECTIVE
  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
  HbA1c(c) 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.
authors: University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, TX 78229-3900, USA.
authors: M
authors: M
authors: Fernandez
authors: A
authors: A
authors: Gastaldelli
authors: C
authors: C
authors: Triplitt
authors: J
authors: J
authors: Hardies
authors: A
authors: A
authors: Casolaro
authors: R
authors: R
authors: Petz
authors: P
authors: P
authors: Tantiwong
authors: N
authors: N
authors: Musi
authors: E
authors: E
authors: Cersosimo
authors: E
authors: E
authors: Ferrannini
authors: R A
authors: RA
authors: DeFronzo