Cardiovascular Effects of Incretin-Based Therapies and Their Therapeutic Potential

Abstract

Antidiabetic drugs with incretin activity in addition to pronounced hypoglycemic activity cause moderate reduction in blood pressure and fat mass as well as improve the lipid profile in patients with type 2 diabetes mellitus (T2DM). In clinical trials the addition of glucagon-like peptide-1 (GLP-1) analogues to standart T2DM therapy leads to significantly reduce the risk of fatal and nonfatal cardiovascular complications. According to the results of many experimental and clinical studies it was shown that GLP-1 analogs protect endothelium in diabetic patients and protect cardiomyocytes after ischemia-reperfusion lesion. Pleiotropic effects of GLP-1-based therapies are realized due to the presence of GLP-1-receptor in endothelial cells, cardiomyocytes, neurons, monocytes and macrophages, as well as due to the connection of the receptor with the most important intracellular signaling cascades (through activation of protein kinase A and B). Whereby GLP-1-based therapies affect the functional condition as well as processes of regeneration and apoptosis of target cells. This review presents the results of studies the cardiovascular effects of GLP-1-based therapies of diabetes. Described proposed nowadays mechanisms of endothelium protective and cardioprotective action of GLP-1 analogs that associated with the action on endothelial function, vascular wall inflammation (the expression of adhesion molecules and inflammatory cytokines), and apoptosis of endothelial cells and cardiomyocytes.