Int J Biol Sci 2021; 17(8):2050-2068. doi:10.7150/ijbs.59965 This issue


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

Xiaoxuan Ma1, Zhenghong Liu1, Iqra Ilyas1, Peter J. Little2,3, Danielle Kamato3, Amirhossein Sahebka4,5, Zhengfang Chen6, Sihui Luo1, Xueying Zheng1, Jianping Weng1✉, Suowen Xu1✉

1. Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China.
2. Sunshine Coast Health Institute, University of the Sunshine Coast, Birtinya, QLD 4575, Australia.
3. School of Pharmacy, Pharmacy Australia Centre of Excellence, the University of Queensland, Woolloongabba, Queensland 4102, Australia.
4. Halal Research Center of IRI, FDA, Tehran, Iran.
5. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad, Iran.
6. Changshu Hospital Affiliated to Soochow University, Changshu No.1 People's Hospital, Changshu 215500, Jiangsu Province, China.

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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. Int J Biol Sci 2021; 17(8):2050-2068. doi:10.7150/ijbs.59965. Available from

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Graphic 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.

Keywords: GLP-1RAs, CVD, diabetes, CVOT, glycemic control, MACE