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

被引:21
作者
Fruchart, Jean-Charles [1 ]
Hermans, Michel P. [2 ,3 ]
Fruchart-Najib, Jamila [1 ]
Kodama, Tatsuhiko [4 ]
机构
[1] Residual Risk Reduct Initiat R3i Fdn, Picassopl 8, CH-4010 Basel, Switzerland
[2] Catholic Univ Louvain, Clin Univ St Luc, Div Endocrinol & Nutr, Brussels, Belgium
[3] Catholic Univ Louvain, Inst Rech Expt & Clin IREC, Brussels, Belgium
[4] Univ Tokyo, Res Ctr Adv Sci & Technol, Lab Syst Biol & Med, Tokyo, Japan
关键词
Pemafibrate; Selective peroxisome proliferator-activated receptor alpha modulator; SPPARM; Triglycerides; Metabolic syndrome; Non-alcoholic fatty liver disease; CORONARY-HEART-DISEASE; BEZAFIBRATE INFARCTION PREVENTION; COMBINATION LIPID THERAPY; TYPE-2; DIABETES-MELLITUS; PPAR-ALPHA; CARDIOVASCULAR-DISEASE; SECONDARY PREVENTION; INSULIN-RESISTANCE; REDUCING TRIGLYCERIDES; FENOFIBRATE THERAPY;
D O I
10.1007/s11883-020-00897-x
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Purpose of Review Adoption 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 alpha) is a therapeutic option. However, current PPAR alpha 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 PPAR alpha receptor, with the aim of maximising beneficial effects and minimising adverse effects, underlies the SPPARM alpha concept. Recent Findings This review discusses the history of SPPARM development, latterly focusing on evidence for the first licensed SPPARM alpha, pemafibrate. Evidence from animal models of hypertriglyceridaemia or NASH, as well as clinical trials in patients with atherogenic dyslipidaemia, are overviewed. The available data set the scene for therapeutic application of SPPARM alpha in the metabolic syndrome, and possibly, NASH. The outstanding question, which has so far eluded fibrates in the setting of current evidence-based therapy including statins, is whether treatment with pemafibrate significantly reduces cardiovascular events in patients with atherogenic dyslipidaemia. The PROMINENT study in patients with type 2 diabetes mellitus and this dyslipidaemia is critical to evaluating this.
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页数:11
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