Tesaglitazar, a dual peroxisome proliferator-activated receptor α/γ agonist, improves apolipoprotein levels in non-diabetic subjects with insulin resistance

Aim: 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 1 mg) 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). Conclusion: Although tesaglitazar is no longer in clinical development, these data indicate that dual PPAR alpha/gamma agonism may be a useful pharmacological approach to improve the atherogenic dyslipidaemia associated with insulin resistance. (C) 2007 Elsevier Ireland Ltd. All rights reserved.