Endocrinol Metab.  2016 Jun;31(2):258-274. 10.3803/EnM.2016.31.2.258.

Cardiovascular Effects of Glucagon-Like Peptide-1 Receptor Agonists

• Kang YM
• Jung CH

• KMID: 2308856
• DOI: http://doi.org/10.3803/EnM.2016.31.2.258

Abstract

Glucagon-like peptide-1 (GLP-1) is a member of the proglucagon incretin family, and GLP-1 receptor agonists (RAs) have been introduced as a new class of antidiabetic medications in the past decade. The benefits of GLP-1 RAs are derived from their pleiotropic effects, which include glucose-dependent insulin secretion, suppressed glucagon secretion, and reduced appetite. Moreover, GLP-1 RAs also exert beneficial roles on multiple organ systems in which the GLP-1 receptors exist, including the cardiovascular system. Cardiovascular effects of GLP-1 RAs have been of great interest since the burden from cardiovascular diseases (CVD) has been unbearably increasing in a diabetic population worldwide, despite strict glycemic control and advanced therapeutic techniques to treat CVD. Preclinical studies have already demonstrated the beneficial effects of GLP-1 on myocardium and vascular endothelium, and many clinical studies evaluating changes in surrogate markers of CVD have suggested potential benefits from the use of GLP-1 RAs. Data from numerous clinical trials primarily evaluating the antihyperglycemic effects of multiple GLP-1 RAs have also revealed that changes in most CVD risk markers reported as secondary outcomes have been in favor of GLP-1 RAs treatment. However, to date, there is only one randomized clinical trial of GLP-1 RAs (the ELIXA study) evaluating major cardiovascular events as their primary outcomes, and in this study, a neutral cardiovascular effect of lixisenatide was observed in high-risk diabetic subjects. Therefore, the results of ongoing CVD outcome trials with the use of GLP-1 RAs should be awaited to elucidate the translation of benefits previously seen in CVD risk marker studies into large clinical trials with primary cardiovascular outcomes.

Keyword

Glucagon-like peptide 1; Cardiovascular; Effect

MeSH Terms

Appetite
Biomarkers
Cardiovascular Diseases
Cardiovascular System
Endothelium, Vascular
Glucagon
Glucagon-Like Peptide 1*
Glucagon-Like Peptide-1 Receptor*
Humans
Incretins
Insulin
Myocardium
Proglucagon
Biomarkers
Glucagon
Glucagon-Like Peptide 1
Glucagon-Like Peptide-1 Receptor
Incretins
Insulin
Proglucagon

Figure

• 

  Fig. 1 Schematic representation of the distribution of glucagon-like peptide-1 (GLP-1) receptors (GLP-1Rs) and the cardiovascular and systemic effects of GLP-1. Modified from Ravassa et al. [25], with permission from Oxford University Press. cAMP, cyclicadenosine monophosphate; cGMP, cyclic guanosine monophosphate; NOS, nitric oxide synthase; PKA, protein kinase A.

• 

  Fig. 2 Classification of currently available glucagon-like peptide-1 receptor agonists (GLP-1 RAs) by structure and duration of action. Adapted from Kuritzky et al. [26], with permission from Taylor & Francis. QW, weekly; QD, daily; BID, twice a day; DPP-4, dipeptidyl peptidase 4; IgG4, immunoglobulin G4.

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