Document Detail


Metabolic effects of muraglitazar in type 2 diabetic subjects.
MedLine Citation:
PMID:  21615671     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M Fernandez; A Gastaldelli; C Triplitt; J Hardies; A Casolaro; R Petz; P Tantiwong; N Musi; E Cersosimo; E Ferrannini; R A DeFronzo
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Diabetes, obesity & metabolism     Volume:  13     ISSN:  1463-1326     ISO Abbreviation:  Diabetes Obes Metab     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-07     Completed Date:  2011-12-07     Revised Date:  2012-02-06    
Medline Journal Info:
Nlm Unique ID:  100883645     Medline TA:  Diabetes Obes Metab     Country:  England    
Other Details:
Languages:  eng     Pagination:  893-902     Citation Subset:  IM    
Copyright Information:
© 2011 Blackwell Publishing Ltd.
Affiliation:
University of Texas Health Science Center and Texas Diabetes Institute, San Antonio, TX 78229-3900, USA.
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MeSH Terms
Descriptor/Qualifier:
Body Mass Index
Diabetes Mellitus, Type 2 / drug therapy*,  metabolism
Female
Glucose Clamp Technique
Glucose Tolerance Test
Glycine / administration & dosage,  analogs & derivatives*,  pharmacology
Hemoglobin A, Glycosylated / drug effects*,  metabolism
Humans
Hypoglycemic Agents / administration & dosage,  pharmacology*
Insulin Resistance
Insulin-Secreting Cells / drug effects*,  metabolism
Intra-Abdominal Fat / drug effects*,  metabolism
Male
Middle Aged
Oxazoles / administration & dosage,  pharmacology*
Peroxisome Proliferator-Activated Receptors / agonists*,  metabolism
Chemical
Reg. No./Substance:
0/Hemoglobin A, Glycosylated; 0/Hypoglycemic Agents; 0/Oxazoles; 0/Peroxisome Proliferator-Activated Receptors; 0/muraglitazar; 56-40-6/Glycine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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