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Incretin drugs as modulators of atherosclerosis

      Highlights

      • Clinical trials show favorable effects of incretin therapy on cardiovascular outcomes.
      • Incretin hormones modulate leukocyte extravasation, endothelial and smooth muscle cell function.
      • The incretin athero-protective role includes blood pressure and lipid profile control.
      • Incretin drugs prevent intima-media dysfunction via anti-inflammatory actions.
      • Incretin treatments for atherosclerosis include GLP-1R agonists and DPP-IV inhibitors.

      Abstract

      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.

      Keywords

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