TY - JOUR
T1 - Metabolic effects of muraglitazar in type 2 diabetic subjects
AU - Fernandez, M.
AU - Gastaldelli, A.
AU - Triplitt, C.
AU - Hardies, J.
AU - Casolaro, A.
AU - Petz, R.
AU - Tantiwong, P.
AU - Musi, N.
AU - Cersosimo, E.
AU - Ferrannini, E.
AU - DeFronzo, Ralph A.
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
KW - Insulin secretion
KW - Insulin sensitivity
KW - Muraglitazar
KW - Muscle/liver/adipocyte
KW - PPARα
KW - PPARγ
KW - Thiazolidinediones
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U2 - 10.1111/j.1463-1326.2011.01429.x
DO - 10.1111/j.1463-1326.2011.01429.x
M3 - Article
C2 - 21615671
AN - SCOPUS:80052537864
SN - 1462-8902
VL - 13
SP - 893
EP - 902
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
IS - 10
ER -