Bempedoic acid: mechanism of action and therapeutic use in atherosclerotic cardiovascular diseases and diabetes

Abstract

Bempedoic acid is a new cholesterol-lowering drug that recently received approval from the US Food and Drug Administration and the European Medicines Agency. This drug targets lipid and glucose metabolism as well as inflammation by downregulating the ATP citrate lyase and upregulating of AMP-activated protein kinase (AMPK). The main effect is to reduce cholesterol synthesis in the liver, and its use is generally not associated with undesirable muscle disorders. Bempedoic acid can reduce the processes of gluconeogenesis, which leads to an improvement in insulin sensitivity, glucose metabolism and features of the metabolic syndrome. The anti-inflammatory effect of bempedoic acid is mainly achieved by activating the AMPK pathway in immune cells, which helps reduce the level of C-reactive protein in plasma. The effects of bempedoic acid on the course of atherosclerotic cardiovascular disease, type2 diabetes and chronic liver disease have been evaluated in randomized clinical trials that require further research. Phase III clinical safety trial show that bempedoic acid is generally well tolerated in combination with statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors in achieving target levels of low-density lipoprotein cholesterol. The aim of this review is to analyze the main mechanisms of action, potential clinical targets of bempedoic acid and describe the existing evidence from clinical trials. The search was done in the Scopus, Science Direct (from Elsevier), and PubMed databases, including the Medline. The following keywords were used: bempedoic acid, low-density lipoprotein cholesterol, atherosclerotic cardiovascular diseases, diabetes. In order to identify research results that could not be found during the online search, a manual search of the bibliography of publications was used.