GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential
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Liu, Z
Ilyas, I
Little, PJ
Kamato, D
Sahebka, A
Chen, Z
Luo, S
Zheng, X
Weng, J
Xu, S
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Abstract
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.
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International Journal of Biological Sciences
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17
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8
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© The author(s) 2021. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
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Medical microbiology
CVD
CVOT
GLP-1RAs
MACE
diabetes
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Ma, X; Liu, Z; Ilyas, I; Little, PJ; Kamato, D; Sahebka, A; Chen, Z; Luo, S; Zheng, X; Weng, J; Xu, S, GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential, International Journal of Biological Sciences, 2021, 17 (8), pp. 2050-2068