GLP-1 Receptor Agonists and Coronary Arteries: From Mechanisms to Events

Abstract

Objective: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) lower plasma glucose through effects on insulin and glucagon secretion and by decelerating gastric emptying. GLP-1 RAs have many beneficial effects beyond glycemic control, including a protective role on the cardiovascular system. However, underlying mechanisms linking GLP-1 RAs with coronary artery disease are complex and not fully elucidated. In this mini-review, we discuss these mechanisms and subsequent clinical events.Data Sources: We searched PubMed and Google Scholar for evidence on GLP-1 RAs and coronary events. We did not apply restrictions on article type. We reviewed publications for clinical relevance.Synopsis of Content: In the first part, we review the current evidence concerning the role of GLP-1 RAs on potential mechanisms underlying the development of coronary events. Specifically, we discuss the role of GLP-1 RAs on atherosclerosis and vasospasms of epicardial coronary arteries, as well as structural/functional changes of coronary microvasculature. In the second part, we summarize the clinical evidence on the impact of GLP-1 RAs in the prevention of acute and chronic coronary syndromes and coronary revascularization. We conclude by discussing existing gaps in the literature and proposing directions for future research.

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“…GLP1 receptors are expressed in endothelial cells, vascular smooth muscle cells, macrophages, and monocytes, supporting an anti-atherosclerotic effect of GLP1-RAs [ 62 , 63 , 64 ]. Indeed, GLP1-RAs decrease reactive oxygen species (ROS) production in endothelial cells and cardiomyocytes and reduce circulating levels of 8-iso prostaglandin and the accumulation of monocytes/macrophages in the vascular wall.…”

Incretins-Based Therapies and Their Cardiovascular Effects: New Game-Changers for the Management of Patients with Diabetes and Cardiovascular Disease

“…Incretins were demonstrated to reduce glucagon concentrations, improve insulin sensitivity, and slow down gastric filling in diabetic patients, with decreased free fatty acid concentrations and body weight. Moreover, beyond glycemic control, incretins protect the cardiovascular system [ 22 ]. The glucose-dependent insulinotropic polypeptide (GIP), a 42 amino acid hormone, and glucagon-like peptide-1 (GLP-1), a 31 amino acid hormone, are the most critical studied incretins.…”

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“…The effect of GLP-1 RAs is glucose-dependent, and they act as multi-target drugs on the (1) stimulation of pancreatic β-cell insulin production, (2) suppression of pancreatic α-cell glucagon secretion, and (3) suppression of hepatic glucagon synthesis with (4) the suppression of gastric emptying time, (5) increased satiety, and (6) increased insulin uptake at the peripheral tissues [ 81 ]. GLP-1 receptor agonists, except for lixisenatide, prevent the development and progression of coronary atherosclerosis, vasospasm of epicardial coronary arteries, and structural/functional changes in coronary microvasculature [ 82 ].…”