Cardiovascular actions of incretin-based therapies

• J.R. Ussher
• Daniel J. Dru

Abstract

Glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors represent 2 distinct classes of incretin-based therapies used for the treatment of type 2 diabetes mellitus. Activation of GLP-1R signaling or inhibition of DPP-4 activity produces a broad range of overlapping and unique cardiovascular actions. Native GLP-1 regulates cardiovascular biology via activation of the classical GLP-1R, or through GLP-1 (9–36), a cardioactive metabolite generated by DPP-4 – mediated cleavage. In contrast, clinically approved GLP1R agonists are not cleaved to GLP-1 (9–36) and produce the majority of their actions through the classical GLP-1R. The cardiovascular mechanisms engaged by DPP-4 inhibition are more complex, encompassing increased levels of intact GLP-1, reduced levels of GLP-1 (9–36), and changes in levels of numerous cardioactive peptides. Herein we review recent experimental and clinical advances that reveal how GLP-1R agonists and DPP-4 inhibitors affect the normal and diabetic heart and coronary vasculature, often independent of changes in blood glucose. Improved understanding of the complex science of incretin-based therapies is required to optimize the selection of these therapeutic agents for the treatment of diabetic patients with cardiovascular disease.

Circ. Res. – 2014. – Vol. 114. – Р. 1788–1803. doi: 10.1161/CIRCRESAHA. 114.301958

Keywords:diabetes mellitus, dipeptidyl peptidase 4, glucagon-like peptide 1, heart, heart failure, myocardial ischemia