MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin PMID: 21752880

ADC Targets in Oncology

2026-04-10

MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin

J Clin Endocrinol Metab. 2011 Sep;96(9):2889-97. doi: 10.1210/jc.2011-1061.

Harold E Bays ¹ , Sherwyn Schwartz , Thomas Littlejohn 3rd , Boris Kerzner , Ronald M Krauss , David B Karpf , Yun-Jung Choi , Xueyan Wang , Sue Naim , Brian K Roberts

Affiliations

Abstract

Context: Preclinical and clinical studies suggest that Peroxisome Proliferator-activated Receptor (PPAR)-δ agonists favorably affect multiple metabolic parameters that are otherwise proatherogenic, many that are not optimally managed with statins alone.

Objective: The aim of this study was to evaluate the effects of MBX-8025 (a novel PPAR-δ agonist) on lipid and Other metabolic parameters associated with increased atherosclerotic risk, administered alone and in combination with atorvastatin.

Design and setting: This was a randomized, double-blind, placebo-controlled, parallel group proof-of-concept study conducted at 30 U.S. research sites.

Participants: This study evaluated 181 overweight men and women with mixed dyslipidemia.

Intervention(s): Subjects were administered once daily placebo, atorvastatin 20 mg, or MBX-8025 at 50 or 100 mg alone or combined with atorvastatin for 8 wk.

Main outcome measures: The main efficacy measures included change from baseline in Apolipoprotein B-100, lipid levels, high-sensitivity C-reactive protein, and additional metabolic parameters, as well as the effect on the metabolic syndrome and LDL particle size.

Results: Compared to placebo, MBX-8025 alone and in combination with atorvastatin significantly (P < 0.05) reduced Apolipoprotein B-100 20-38%, LDL 18-43%, triglycerides 26-30%, non-high-density lipoprotein Cholesterol 18-41%, free fatty acids 16-28%, and high-sensitivity C-reactive protein 43-72%; it raised high-density lipoprotein Cholesterol 1-12% and also reduced the number of patients with the metabolic syndrome and a preponderance of small LDL particles. MBX-8025 was safe and generally well-tolerated. MBX-8025 also reduced liver enzyme levels.

Conclusion: MBX-8025, a novel PPAR-δ agonist, favorably affected multiple metabolic parameters with and without atorvastatin. A more complete understanding of MBX-8025 requires a larger future study.