GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential

• Published in: International journal of biological sciences Vol. 17; no. 8; pp. 2050 - 2068
• Main Authors: Ma, Xiaoxuan, Liu, Zhenghong, Ilyas, Iqra, Little, Peter J., Kamato, Danielle, Sahebka, Amirhossein, Chen, Zhengfang, Luo, Sihui, Zheng, Xueying, Weng, Jianping, Xu, Suowen
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2021; Ivyspring International Publisher
• Subjects: Agonists; Angina pectoris; Animal models; Arteriosclerosis; Atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - metabolism; Blood pressure; Cardiomyocytes; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - prevention & control; Cell culture; Clinical trials; Congestive heart failure; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Disease prevention; Drug therapy; Endothelial cells; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide-1 Receptor - agonists; Glucagon-Like Peptide-1 Receptor - metabolism; Glucose; Hemoglobin; Humans; Hypertension; Hypoglycemia; Hypoglycemic Agents - pharmacology; Inflammation; Insulin; Insulin secretion; Ischemia; Kinases; Lipids; Macrophages; Molecular modelling; Monocytes; Mortality; Muscles; Proteins; Receptors; Review; Risk factors; Side effects; Smooth muscle; CVD; glycemic control; MACE; diabetes; CVOT; GLP-1RAs
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.59965

Type 2 diabetes mellitus (T2DM) is closely associated with cardiovascular diseases (CVD), including atherosclerosis, hypertension and heart failure. Some anti-diabetic medications are linked with an increased risk of weight gain or hypoglycemia which may reduce the efficacy of the intended anti-hyperglycemic effects of these therapies. The recently developed receptor agonists for glucagon-like peptide-1 (GLP-1RAs), stimulate insulin secretion and reduce glycated hemoglobin levels without having side effects such as weight gain and hypoglycemia. In addition, GLP1-RAs demonstrate numerous cardiovascular protective effects in subjects with or without diabetes. There have been several cardiovascular outcomes trials (CVOTs) involving GLP-1RAs, which have supported the overall cardiovascular benefits of these drugs. GLP1-RAs lower plasma lipid levels and lower blood pressure (BP), both of which contribute to a reduction of atherosclerosis and reduced CVD. GLP-1R is expressed in multiple cardiovascular cell types such as monocyte/macrophages, smooth muscle cells, endothelial cells, and cardiomyocytes. Recent studies have indicated that the protective properties against endothelial dysfunction, anti-inflammatory effects on macrophages and the anti-proliferative action on smooth muscle cells may contribute to atheroprotection through GLP-1R signaling. In the present review, we describe the cardiovascular effects and underlying molecular mechanisms of action of GLP-1RAs in CVOTs, animal models and cultured cells, and address how these findings have transformed our understanding of the pharmacotherapy of T2DM and the prevention of CVD.