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GLP-1 receptor agonists (GLP-1RAs): cardiovascular actions and therapeutic potential
Journal article   Open access   Peer reviewed

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

Xiaoxuan Ma, Zhenghong Lui, Iqra Ilyas, Peter James Little, Danielle Kamato, Amirhossein Sahebkar, Zhengfang Chen, Sihui Luo, Xueying Zheng, Jianping Weng, …
International Journal of Biological Sciences, Vol.17(8), pp.2050-2068
2021
PMCID: PMC8193264
PMID: 34131405
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GLP-1 receptor agonists (GLP-1RAs) - cardiovascular actions and therapeutic potential1.15 MBDownloadView
Published Version Open Access CC BY V4.0
url
https://doi.org/10.7150/ijbs.59965View
Published Version

Abstract

Diabetes GLP-1RAs CVD CVOT glycemic control MACE
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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