Document Detail


The dual peroxisome proliferator-activated receptor alpha/gamma agonist tesaglitazar further improves the lipid profile in dyslipidemic subjects treated with atorvastatin.
MedLine Citation:
PMID:  17697874     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Tesaglitazar (GALIDA; AstraZeneca, Wilmington, DE) is a dual peroxisome proliferator-activated receptor alpha/gamma agonist previously in clinical development for the treatment of glucose and lipid abnormalities associated with type 2 diabetes mellitus and insulin resistance. This study compared the efficacy of tesaglitazar with that of pioglitazone as adjunctive therapy to atorvastatin in subjects with abdominal obesity and dyslipidemia. In this open-label, 3-way crossover study, 58 subjects received atorvastatin 10 mg once daily in a 6-week run-in period, followed by tesaglitazar 3 mg, pioglitazone 45 mg, or placebo, as adjunctive therapy to atorvastatin, in a randomized sequence for 6 weeks each. Serum triglycerides and other lipids, apolipoproteins, glucose, and insulin concentrations were compared between treatments. Tesaglitazar adjunctive therapy reduced serum triglycerides significantly more from baseline (-1.07 mmol/L) than pioglitazone (-0.33 mmol/L; P = .007) or placebo (-0.09 mmol/L; P < .0001). Tesaglitazar also resulted in significantly greater improvements in free fatty acids, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio, low-density lipoprotein particle size, apolipoprotein (apo) B, apo C-III, and the apo B/apo A-I ratio compared with pioglitazone or placebo. Tesaglitazar adjunctive therapy also reduced fasting plasma glucose, fasting plasma insulin, and insulin resistance (homeostasis model assessment index) significantly more than pioglitazone or placebo (P < .0001 for all comparisons). Tesaglitazar was generally well tolerated in combination with atorvastatin, but hemoglobin and absolute neutrophil count decreased and serum creatinine increased more with tesaglitazar than with pioglitazone or placebo. These effects, also shown in previous trials, led to the discontinuation of the clinical development of the drug. In conclusion, the addition of tesaglitazar to a background of atorvastatin therapy further improved the dyslipidemia associated with insulin resistance.
Authors:
Serena Tonstad; Kjetil Retterstøl; Leiv Ose; K Peter Ohman; Magnus B Lindberg; Maria Svensson
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Publication Detail:
Type:  Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  56     ISSN:  0026-0495     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-16     Completed Date:  2007-10-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1285-92     Citation Subset:  IM    
Affiliation:
Department of Preventive Cardiology, Ullevål University Hospital, N-0407, Oslo, Norway. serena.tonstad@uus.no
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MeSH Terms
Descriptor/Qualifier:
Adult
Alkanesulfonates / administration & dosage*,  pharmacology*
Anticholesteremic Agents / therapeutic use
Chemotherapy, Adjuvant
Cross-Over Studies
Drug Combinations
Drug Synergism
Dyslipidemias / drug therapy*
Female
Heptanoic Acids / therapeutic use*
Humans
Hypoglycemic Agents / administration & dosage
Lipids / blood*
Male
Middle Aged
PPAR alpha / agonists*
PPAR gamma / agonists*
Phenylpropionates / administration & dosage*,  pharmacology*
Placebos
Pyrroles / therapeutic use*
Thiazolidinediones / administration & dosage
Chemical
Reg. No./Substance:
0/2-ethoxy-3-(4-((4-(methylsulfonyloxy)phenethyl)oxy)phenyl)propanoic acid; 0/Alkanesulfonates; 0/Anticholesteremic Agents; 0/Drug Combinations; 0/Heptanoic Acids; 0/Hypoglycemic Agents; 0/Lipids; 0/PPAR alpha; 0/PPAR gamma; 0/Phenylpropionates; 0/Placebos; 0/Pyrroles; 0/Thiazolidinediones; 110862-48-1/atorvastatin; 111025-46-8/pioglitazone

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