GLP-1 Receptor Agonists and Cardiovascular Disease in Patients with Type 2 Diabetes

Abstract

Diabetes mellitus is a chronic disease prevalence of which is high and continually growing. Cardiovascular disease continues to be the leading cause of death in patients with T2DM. The prevention of cardiovascular complications and the cardiovascular safety of treatments should be a primary objective when selecting treatment. Among all the drugs available, the compounds known as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) appear to be not just innocuous in terms of CVD but indeed to be beneficial. GLP-1 RA actions not only translate on an improvement of well-known cardiovascular risk factors such as glycaemic control, dyslipidaemia, weight, or arterial hypertension but also might show benefits on endothelial function, coronary ischaemia, and heart failure. On the other hand, recent clinical trials aimed at studying cardiovascular episodes have been conducted with GLP-1 RAs. Only liraglutide and semaglutide have shown superiority in cardiovascular benefit compared with placebo. Although many of the mechanisms by which liraglutide and semaglutide produce a cardiovascular benefit are still unknown it would be desirable for these benefits to be incorporated into the therapeutic algorithms routinely used in clinical practice. The purpose of this review is to explore GLP-1 RA actions not only in cardiovascular risk factors (glucose, weight, and hypertension) but also the possible effects on established cardiovascular disease.

Advances in type 2 diabetes therapy: a focus on cardiovascular and renal outcomes

“…The mechanism by which GLP1 receptor agonists influence cardiovascular outcome is not well understood. These agents have weight‐reducing effects and cause a modest reduction in systolic blood pressure of about 2–3 mmHg, probably through natriuresis, improved endothelial function, and vasodilation . The blood pressure reduction is accompanied by an increase in heart rate, and whether this influences cardiovascular outcomes remains uncertain.…”

“…These agents have weight-reducing effects and cause a modest reduction in systolic blood pressure of about 2-3 mmHg, 34,35 probably through natriuresis, improved endothelial function, and vasodilation. 36,37 The blood pressure reduction is accompanied by an increase in heart rate, 38 and whether this influences cardiovascular outcomes remains uncertain. There is some evidence that GLP1 receptor agonists may modulate inflammation and have other beneficial effects for atherosclerosis and cardiovascular disease beyond their metabolic profile.…”

DIAGNOSIS OF ENDOCRINE DISEASE: Drug-induced endocrinopathies and diabetes: a combo-endocrinology overview

“…Most studies investigating the impact on lipid profile were performed with either liraglutide or exenatide in healthy subjects and in patients with T2DM and showed significant reduction of fasting and postprandial chylomicron TG levels, modest decreases in TC and LDLc and small or no significant change in HDLc levels (195). In the case of liraglutide, it seems that there is direct effect of the drug on the expression of genes involved in the biosynthesis of chylomicron and a reduction of APOB48 pool (194,196).…”

The protective effects of GLP-1 receptor agonist lixisenatide on oxygen-glucose deprivation/reperfusion (OGD/R)-induced deregulation of endothelial tube formation

“…11 Recent studies have shown that GLP-1 agonists have pleiotropic effects that can modulate cardiovascular complications, such as increasing heart rate, reducing blood pressure, and improving myocardial infarction and vascular endothelial function. [12][13][14] Lixisenatide is an improved shortacting GLP-1 receptor agonist widely used in clinical practice. Lixisenatide was developed based on the structure of the earlier GLP-1 analog exendin-4.…”