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 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). CONCLUSION: 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.
RCT Entities:
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 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). CONCLUSION: 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: J W A van der Hoorn; J W Jukema; L M Havekes; E Lundholm; G Camejo; P C N Rensen; H M G Princen Journal: Br J Pharmacol Date: 2009-02-13 Impact factor: 8.739
Authors: Dustin K Bauknight; Victoria Osinski; Siva Sai Krishna Dasa; Anh T Nguyen; Melissa A Marshall; Julia Hartman; Matthew Harms; Gavin O'Mahony; Jeremie Boucher; Alexander L Klibanov; Coleen A McNamara; Kimberly A Kelly Journal: PLoS One Date: 2019-11-14 Impact factor: 3.240
Authors: Victoria Osinski; Dustin K Bauknight; Siva Sai Krishna Dasa; Matthew J Harms; Tobias Kroon; Melissa A Marshall; James C Garmey; Anh T Nguyen; Julia Hartman; Aditi Upadhye; Prasad Srikakulapu; Andrea Zhou; Gavin O'Mahony; Alexander L Klibanov; Kimberly A Kelly; Jeremie Boucher; Coleen A McNamara Journal: Theranostics Date: 2020-01-01 Impact factor: 11.556