Selective Peroxisome Proliferator-Activated Receptor Alpha Modulators (SPPARM α) in the Metabolic Syndrome: Is Pemafibrate Light at the End of the Tunnel?

AbstractPurpose of ReviewAdoption of poor lifestyles (inactivity and energy-dense diets) has driven the worldwide increase in the metabolic syndrome, type 2 diabetes mellitus and non-alcoholic steatohepatitis (NASH). Of the defining features of the metabolic syndrome, an atherogenic dyslipidaemia characterised by elevated triglycerides (TG) and low plasma concentration of high-density lipoprotein cholesterol is a major driver of risk for atherosclerotic cardiovascular disease. Beyond lifestyle intervention and statins, targeting the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR α) is a therapeutic option. However, current PPARα agonists (fibrates) have limitations, including safety issues and the lack of definitive evidence for cardiovascular benefit. Modulating the ligand structure to enhance binding at the PPARα receptor, with the aim of maximising beneficial effects and minimising adverse effects, underlies the SPPARMα concept.Recent FindingsThis review discusses the history of SPPARM development, latterly focusing on evidence for the first licensed SPPARM α, pemafibrate. Evidence from animal models of hypertriglyceridaemia or NASH, as well as clinical trials in patients with atherogenic dyslipidaemia, are overviewed.SummaryThe available data set the scene for therapeutic application of SPPARM α in the metabolic syndrome, and possibly, NASH. The outstanding question, which has so far eluded fibrates in the setting of current evidence-based t...
Source: Current Atherosclerosis Reports - Category: Cardiology Source Type: research