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Expert Opin Pharmacother. 2014 Mar;15(4):493-503. doi: 10.1517/14656566.2014.876992. Epub 2014 Jan 16.

New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease.

Author information

1
Biotechnology Research Center, Mashhad University of Medical Sciences , Mashhad , Iran.

Abstract

INTRODUCTION:

Novel peroxisome proliferator-activated receptor (PPAR) modulators (selective PPAR modulators [SPPARMs]) and dual PPAR agonists may have an important role in the treatment of cardiometabolic disorders owing to lipid-modifying, insulin-sensitizing and anti-inflammatory effects.

AREAS COVERED:

This review summarizes the efficacy of new PPAR agonists and SPPARMs that are under development for the treatment of atherogenic dyslipidemia and non-alcoholic fatty liver disease (NAFLD).

EXPERT OPINION:

ABT-335 is a new formulation of fenofibrate that has been approved for concomitant use with statins. K-877, a SPPARM-α with encouraging preliminary results in modulating atherogenic dyslipidemia, and INT131, a SPPARM-γ with predominantly insulin-sensitizing actions, may also have favorable lipid-modifying effects. Although the development of dual PPAR-α/γ agonists (glitazars) and the SPPARM-δ GW501516 has been abandoned because of safety issues, another SPPARM-δ (MBX-8025) and a dual PPAR-α/δ agonist (GFT-505) have shown promising efficacy in decreasing plasma triglyceride and increasing high-density lipoprotein cholesterol concentrations, as well as improving insulin sensitivity and liver function. The beneficial effects of GFT-505 are complemented by preclinical findings that indicate reduction of hepatic fat accumulation, inflammation and fibrosis, making it a promising candidate for the treatment of NAFLD/nonalcoholic steatohepatitis (NASH). Long-term trials are required to test the efficacy and safety of these new PPAR agonists in reducing cardiovascular outcomes and treating NAFLD/NASH.

PMID:
24428677
DOI:
10.1517/14656566.2014.876992
[Indexed for MEDLINE]

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