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Metabolic effects of muraglitazar in type 2 diabetic subjects
Author(s) -
Fernandez M.,
Gastaldelli A.,
Triplitt C.,
Hardies J.,
Casolaro A.,
Petz R.,
Tantiwong P.,
Musi N.,
Cersosimo E.,
Ferrannini E.,
DeFronzo R. A.
Publication year - 2011
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2011.01429.x
Subject(s) - medicine , endocrinology , adiponectin , insulin resistance , type 2 diabetes , insulin , adipose tissue , triglyceride , diabetes mellitus , cholesterol
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: 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.