Effects of the PPAR-δ agonist MBX-8025 on atherogenic dyslipidemia

Atherosclerosis. 2012 Feb;220(2):470-6. doi: 10.1016/j.atherosclerosis.2011.10.029. Epub 2011 Nov 16.

Abstract

Objective: Determine the effects of treatment with a selective PPAR-δ agonist±statin on plasma lipoprotein subfractions in dyslipidemic individuals.

Methods: Ion mobility analysis was used to measure plasma concentrations of subfractions of the full spectrum of lipoprotein particles in 166 overweight or obese dyslipidemic individuals treated with the PPAR-δ agonist MBX-8025 (50 and 100 mg/d)±atorvastatin (20 mg/d) in an 8-week randomized parallel arm double blind placebo controlled trial.

Results: MBX-8025 at both doses resulted in reductions of small plus very small LDL particles and increased levels of large LDL, with a concomitant reduction in large VLDL, and an increase in LDL peak diameter. This translated to reversal of the small dense LDL phenotype (LDL pattern B) in ∼90% of the participants. Modest increases in HDL particles were confined to the smaller HDL fractions. Atorvastatin monotherapy resulted in reductions in particles across the VLDL-IDL-LDL spectrum, with a significantly smaller reduction in small and very small LDL vs. MBX-8025 100 mg/d (-24.5±5.3% vs. -47.8±4.9%), and, in combination with MBX-8025, a reversal of the increase in large LDL.

Conclusion: PPAR-δ and statin therapies have complementary effects in improving lipoprotein subfractions associated with atherogenic dyslipidemia.

Trial registration: ClinicalTrials.gov NCT00701883.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / therapeutic use*
  • Analysis of Variance
  • Atherosclerosis / blood
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / etiology
  • Atorvastatin
  • Biomarkers / blood
  • Chi-Square Distribution
  • Double-Blind Method
  • Drug Therapy, Combination
  • Dyslipidemias / blood
  • Dyslipidemias / complications
  • Dyslipidemias / drug therapy*
  • Female
  • Heptanoic Acids / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypolipidemic Agents / therapeutic use*
  • Lipoproteins / blood*
  • Male
  • Middle Aged
  • Obesity / complications
  • Overweight / complications
  • PPAR gamma / agonists*
  • PPAR gamma / metabolism
  • Particle Size
  • Pyrroles / therapeutic use
  • Time Factors
  • Treatment Outcome
  • Triazoles / therapeutic use*

Substances

  • (2-methyl-4-(5-methyl-2-(4-trifluoromethyl-phenyl)-2H-(1,2,3)triazol-4-ylmethylsulfanyl)phenoxy)acetic acid
  • Acetates
  • Biomarkers
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Lipoproteins
  • PPAR gamma
  • Pyrroles
  • Triazoles
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT00701883