Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma agonist, improves apolipoprotein levels in non-diabetic subjects with insulin resistance.
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.
Schuster
Herbert
H
Humboldt University, Berlin, Germany. herbert.schuster@infogen.de
Fagerberg
Björn
B
Edwards
Siôn
S
Halmos
Tamas
T
Lopatynski
Jerzy
J
Stender
Steen
S
Birketvedt
Grethe Stoa
GS
Tonstad
Serena
S
Gause-Nilsson
Ingrid
I
Halldórsdóttir
Sigrún
S
Ohman
K Peter
KP
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*
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