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Review
. 2024 Sep 19;263(1):e240046.
doi: 10.1530/JOE-24-0046. Print 2024 Oct 1.

GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms

Neerav Mullur  1 , Arianne Morissette  2 , Nadya M Morrow  2   3 , Erin E Mulvihill  2   3
Affiliations
Review

GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms

Neerav Mullur et al. J Endocrinol. .

Abstract

Cardiovascular outcome trials (CVOTs) in people living with type 2 diabetes mellitus and obesity have confirmed the cardiovascular benefits of glucagon-like peptide 1 receptor agonists (GLP-1RAs), including reduced cardiovascular mortality, lower rates of myocardial infarction, and lower rates of stroke. The cardiovascular benefits observed following GLP-1RA treatment could be secondary to improvements in glycemia, blood pressure, postprandial lipidemia, and inflammation. Yet, the GLP-1R is also expressed in the heart and vasculature, suggesting that GLP-1R agonism may impact the cardiovascular system. The emergence of GLP-1RAs combined with glucose-dependent insulinotropic polypeptide and glucagon receptor agonists has shown promising results as new weight loss medications. Dual-agonist and tri-agonist therapies have demonstrated superior outcomes in weight loss, lowered blood sugar and lipid levels, restoration of tissue function, and enhancement of overall substrate metabolism compared to using GLP-1R agonists alone. However, the precise mechanisms underlying their cardiovascular benefits remain to be fully elucidated. This review aims to summarize the findings from CVOTs of GLP-1RAs, explore the latest data on dual and tri-agonist therapies, and delve into potential mechanisms contributing to their cardioprotective effects. It also addresses current gaps in understanding and areas for further research.

Keywords: cardiovascular; hormone action; incretins; metabolism; nutrition.

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Conflict of interest statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Figures

Figure 1
Figure 1
Cardiovascular benefits of GLP-1RA, dual, or triple agonists. (A) Distribution of Glp1r or GLP1R (in black), Gipr or GIPR (in blue), and Gcgr or GCGR (in green) mRNA in the heart of humans and mice. (B) Mechanisms of action by which GLP-1RA (black), dual (blue), or triple agonists (green) improve cardiovascular outcomes. GLP-1RA, glucagon-like peptide 1 receptor agonist; GIPR, glucose-dependent insulinotropic peptide receptor; GCGR, glucagon receptor; TG, triglycerides; VLDL, very low-density lipoproteins; AMPK, 5' adenosine monophosphate-activated protein kinase.
See this image and copyright information in PMC

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