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Author: Nadya M Morrow x

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

Neerav Mullur

Neerav Mullur The University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada

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Arianne Morissette

Arianne Morissette The University of Ottawa Heart Institute, Ottawa, Ontario, Canada

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Nadya M Morrow

Nadya M Morrow The University of Ottawa Heart Institute, Ottawa, Ontario, Canada
Department of Biochemistry, Microbiology and Immunology, The University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada

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Erin E Mulvihill

Erin E Mulvihill The University of Ottawa Heart Institute, Ottawa, Ontario, Canada
Department of Biochemistry, Microbiology and Immunology, The University of Ottawa, Faculty of Medicine, Ottawa, Ontario, Canada

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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.