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The effect of glucagon-like peptide 1 on cardiovascular risk

Abstract

Glucagon-like peptide 1 (GLP-1) is an incretin hormone responsible for amplification of insulin secretion when nutrients are given orally, as opposed to intravenously, and it retains its insulinotropic activity in patients with type 2 diabetes mellitus. GLP-1-based therapies, such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase 4, an enzyme that degrades endogenous GLP-1, have established effectiveness in lowering glucose levels and are routinely used to treat patients with type 2 diabetes. These agents regulate glucose metabolism through multiple mechanisms and have several effects on cardiovascular parameters. These effects, possibly independent of the glucose-lowering activity, include changes in blood pressure, endothelial function, body weight, cardiac metabolism, lipid metabolism, left ventricular function, atherosclerosis, and the response to ischemia–reperfusion injury. Thus, GLP-1-based therapies could potentially target both diabetes and cardiovascular disease. This Review highlights the mechanisms targeted by GLP-1-based therapies, and emphasizes current developments in incretin research that are relevant to cardiovascular risk and disease, as well as treatment with GLP-1 receptor agonists.

Key Points

  • Glucagon-like peptide 1 receptor (GLP-1R) agonists lower blood pressure in patients with type 2 diabetes mellitus

  • GLP-1R agonists have a long-term, weight-reducing effect in the majority of patients with type 2 diabetes

  • Ischemic preconditioning and postconditioning with GLP-1R agonists results in a reduction of ≤50% in the size of myocardial infarctions in animal models, and inhibit myocardial stunning and dysfunction in humans

  • GLP-1R agonists reduce the levels of biomarkers that have been linked to atherosclerotic cardiovascular disease and, therefore, might inhibit atherosclerosis development

  • GLP-1R agonists might improve endothelial dysfunction

  • To date, clinical studies of GLP-1R agonists have shown improvement, rather than impairment, in cardiovascular parameters

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Figure 1: Different post-translational processing of proglucagon in the pancreas, gut, and brain.
Figure 2: How GLP-1 might regulate blood pressure.
Figure 3: The effect of GLP-1R agonist treatment on systolic blood pressure.
Figure 4: The effect of GLP-1R agonist treatment on body weight.

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J. Sivertsen, T. Vilsbøll and J. J. Holst contributed to all aspects of the article, including researching data, discussion of content, and writing, reviewing, and editing the manuscript before submission.

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Correspondence to Jens J. Holst.

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J. Sivertsen declares no competing interests. J. Rosenmeier declares that she has received grant support from Merck Sharp & Dohme. J. J. Holst declares that he has been a consultant for GlaxoSmithKline, Novo Nordisk, and Zealand Pharmaceuticals. He has also received grants from Merck Sharp & Dohme and Novartis. T. Vilsbøll declares that she has been a consultant for and received honoraria from Amylin, Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Sharp & Dohme, Novo Nordisk, and Sanofi. She has also received honoraria from Novartis, and grant support from Merck Sharp & Dohme.

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Sivertsen, J., Rosenmeier, J., Holst, J. et al. The effect of glucagon-like peptide 1 on cardiovascular risk. Nat Rev Cardiol 9, 209–222 (2012). https://doi.org/10.1038/nrcardio.2011.211

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