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Incretin-based therapies for the failing heart

Ussher, John R.; Campbell, Jonathan E.

doi: 10.1097/XCE.0000000000000086
Review Articles

The gut incretin hormone, glucagon-like peptide 1 (GLP-1), regulates islet hormone secretion, circulating glucose levels, and body weight, making it an attractive agent for the treatment of type 2 diabetes. As cardiovascular disease represents the leading cause of death in patients with diabetes, it is important to understand how GLP-1-based drugs impact the cardiovascular system. Here, we review recent advances in our understanding of two incretin-based drug classes, GLP-1 receptor agonists and dipeptidyl peptidase 4 inhibitors, specifically in the context of heart failure. In addition to illustrating how these therapies influence cardiac signaling processes, we describe the cardioprotective mechanisms identified in preclinical studies, while reviewing the clinical data from studies in patients with type 2 diabetes. We end by speculating why observations made in preclinical studies are not necessarily reflected in a clinically relevant patient population.

aFaculty of Pharmacy and Pharmaceutical Sciences

bAlberta Diabetes Institute

cMazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada

dDuke Molecular Physiology Institute

Departments of eMedicine

fPharmacology and Cancer Biology, Duke University, Durham, North Carolina, USA

Correspondence to Jonathan E. Campbell, PhD, 300 N Duke Street, Duke University, Durham, NC 27701, USA Tel: +1 919 684 4865; fax: +1 919 684 0905; e-mail:

Received May 4, 2016

Accepted June 23, 2016

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.