Incretin drugs as modulators of atherosclerosis

Atherosclerosis is a major underlying cause of ischemic heart diseases, ischemic stroke, and peripheral artery disease. Atherosclerotic plaque progression is characterized by chronic progressive inflammation of the arterial wall, endothelial cell dysfunction, and subendothelial lipoprotein retention. Incretin drugs, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase-IV (DPP-IV) inhibitors, are promising anti-hyperglycemic agents used for the treatment of type 2 diabetes mellitus (T2DM). In addition to glucose-lowering effects, emerging data suggest that incretin drugs have anti-atherogenic effects with the potential to stabilize atherosclerotic plaques and treat arterial inflammation. Clinical and preclinical studies have reported a plethora of therapeutic benefits of incretin drugs, including modulation of inflammatory response, reduction of intima-media thickening, improvement in lipid profiles, endothelial and smooth muscle cell modulation. Despite extensive research and widespread clinical use of incretin-based therapies, the research on the incretin hormones continues to expand. This review outlines clinical studies, molecular aspects, and potential therapeutic implications of incretin drugs in attenuation of atherosclerosis.