New Agents for Treatment of Dyslipidemia

Diabetes mellitus is associated with elevated risk for atherosclerotic cardiovascular disease (ASCVD), and statin therapy has been shown to reduce this risk. ASCVD is leading cause for morbidity and mortality in patients with type 2 diabetes, and heartening trend of decreasing ASCVD mortality in the overall population is unfortunately not seen in patients with diabetes. This chapter summarizes the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in regulation of circulating cholesterol levels, clinical trials of PCSK9 inhibitors, and their optimal use in clinical practice, followed by a brief discussion on emerging triglyceride-lowering therapies. The net effect of PCSK9 is reduced recycling of low density lipoprotein (LDL) receptor to the hepatocyte membrane and resultant decrease in clearance of circulating LDL particles. The available data clearly show the ability of this class of lipid-lowering drugs to safely and effectively reduce the level of LDL-cholesterol and other atherogenic lipoproteins leading to reduced incidence of major vascular events.