title: Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma agonist, improves apolipoprotein levels in non-diabetic subjects with insulin resistance.
abstract: OBJECTIVE
  To determine the effects of the peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist tesaglitazar on serum levels of apolipoprotein (apo) A-I, apoB, and apoCIII in non-diabetic insulin-resistant subjects.
  
  
  METHODS
  This randomized, double-blind, multicentre, placebo-controlled trial examined the effect of tesaglitazar (0.1, 0.25, 0.5, and 1mg) once daily for 12 weeks on apolipoprotein levels in 390 abdominally obese subjects with hypertriglyceridaemia.
  
  
  RESULTS
  Tesaglitazar dose-dependently increased serum concentrations of apoA-I (p<0.009) and decreased concentrations of apoB (p<0.0001), the apoB/apoA-I ratio (p<0.0001), and apoCIII (p<0.0001). Similar improvements were observed in all subgroups of subjects, where individuals were grouped according to age, gender, baseline body mass index, serum triglycerides and high-density lipoprotein cholesterol levels. Low-density lipoprotein particle concentrations were also dose-dependently reduced by tesaglitazar (p<0.0001).
  
  
  CONCLUSIONS
  Although tesaglitazar is no longer in clinical development, these data indicate that dual PPARalpha/gamma agonism may be a useful pharmacological approach to improve the atherogenic dyslipidaemia associated with insulin resistance.
authors.affiliation: Humboldt University, Berlin, Germany. herbert.schuster@infogen.de
authors.forename: Herbert
authors.initials: H
authors.lastname: Schuster
authors.forename: Björn
authors.initials: B
authors.lastname: Fagerberg
authors.forename: Siôn
authors.initials: S
authors.lastname: Edwards
authors.forename: Tamas
authors.initials: T
authors.lastname: Halmos
authors.forename: Jerzy
authors.initials: J
authors.lastname: Lopatynski
authors.forename: Steen
authors.initials: S
authors.lastname: Stender
authors.forename: Grethe Stoa
authors.initials: GS
authors.lastname: Birketvedt
authors.forename: Serena
authors.initials: S
authors.lastname: Tonstad
authors.forename: Ingrid
authors.initials: I
authors.lastname: Gause-Nilsson
authors.forename: Sigrún
authors.initials: S
authors.lastname: Halldórsdóttir
authors.forename: K Peter
authors.initials: KP
authors.lastname: Ohman
mesh_terms: D000328:Adult; D000368:Aged; D000476:Alkanesulfonates / Q000008:administration & dosage*; D016632:Apolipoprotein A-I / Q000097:blood; D053305:Apolipoprotein C-III / Q000097:blood; D001053:Apolipoproteins / Q000097:blood*; D001055:Apolipoproteins B / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010666:Phenylpropionates / Q000008:administration & dosage*
chemical_list: D000476:Alkanesulfonates; D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D047493:PPAR alpha; D047495:PPAR gamma; D010666:Phenylpropionates; C501413:tesaglitazar