• DOI:10.1517/14656566.2014.876992
• Corpus ID: 21158696

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

@article{Sahebkar2014NewPP,
  title={New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease},
  author={Amirhossein Sahebkar and Gerard T. Chew and Gerald F. Watts},
  journal={Expert Opinion on Pharmacotherapy},
  year={2014},
  volume={15},
  pages={493 - 503}
}

• A. Sahebkar, G. Chew, G. Watts
• Published 8 February 2014
• Medicine, Biology
• Expert Opinion on Pharmacotherapy

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.