Metabolic effects of muraglitazar in type 2 diabetic subjects

M. Fernandez, A. Gastaldelli, Curtis L Triplitt, J. Hardies, A. Casolaro, R. Petz, P. Tantiwong, Nicolas Musi, Eugenio Cersosimo, E. Ferrannini, Ralph A Defronzo

Research output: Contribution to journalArticle

9 Citations (Scopus)

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

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Type 2 Diabetes Mellitus
Placebos
Intra-Abdominal Fat
Insulin Resistance
Liver
Muscles
Adipose Tissue
Abdominal Subcutaneous Fat
Diet
Peroxisome Proliferator-Activated Receptors
Glucose Clamp Technique
muraglitazar
Adiponectin
Glucose Tolerance Test
Body Composition
Nonesterified Fatty Acids
LDL Cholesterol
HDL Cholesterol
Weight Gain
Weight Loss

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Fernandez, M., Gastaldelli, A., Triplitt, C. L., Hardies, J., Casolaro, A., Petz, R., ... Defronzo, R. A. (2011). Metabolic effects of muraglitazar in type 2 diabetic subjects. Diabetes, Obesity and Metabolism, 13(10), 893-902. https://doi.org/10.1111/j.1463-1326.2011.01429.x

Metabolic effects of muraglitazar in type 2 diabetic subjects. / Fernandez, M.; Gastaldelli, A.; Triplitt, Curtis L; Hardies, J.; Casolaro, A.; Petz, R.; Tantiwong, P.; Musi, Nicolas; Cersosimo, Eugenio; Ferrannini, E.; Defronzo, Ralph A.

In: Diabetes, Obesity and Metabolism, Vol. 13, No. 10, 10.2011, p. 893-902.

Research output: Contribution to journalArticle

Fernandez, M, Gastaldelli, A, Triplitt, CL, Hardies, J, Casolaro, A, Petz, R, Tantiwong, P, Musi, N, Cersosimo, E, Ferrannini, E & Defronzo, RA 2011, 'Metabolic effects of muraglitazar in type 2 diabetic subjects', Diabetes, Obesity and Metabolism, vol. 13, no. 10, pp. 893-902. https://doi.org/10.1111/j.1463-1326.2011.01429.x
Fernandez M, Gastaldelli A, Triplitt CL, Hardies J, Casolaro A, Petz R et al. Metabolic effects of muraglitazar in type 2 diabetic subjects. Diabetes, Obesity and Metabolism. 2011 Oct;13(10):893-902. https://doi.org/10.1111/j.1463-1326.2011.01429.x
Fernandez, M. ; Gastaldelli, A. ; Triplitt, Curtis L ; Hardies, J. ; Casolaro, A. ; Petz, R. ; Tantiwong, P. ; Musi, Nicolas ; Cersosimo, Eugenio ; Ferrannini, E. ; Defronzo, Ralph A. / Metabolic effects of muraglitazar in type 2 diabetic subjects. In: Diabetes, Obesity and Metabolism. 2011 ; Vol. 13, No. 10. pp. 893-902.
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AU - Petz, R.

AU - Tantiwong, P.

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