Cardiac Protection via Metabolic Modulation: An Emerging Role for Incretin-Based Therapies?

Liam      M. McCormick; Anna      C. Kydd; David      P. Dutka

Abstract

Cardiovascular disease continues to be a major cause of morbidity and mortality in patients with Type 2 Diabetes Mellitus. Whilst a focus on improved glucose control and HbA1c has led to a reduction in the progression and development of microvascular complications, the potential for this strategy to reduce cardiovascular event rates is less clearly defined. Identification of the incretin axis has facilitated the development of several novel therapeutic agents which target glucagon-like peptide-1 (GLP-1) pathways. The effects on glucose homeostasis are now established, but there is also now an increasing body of evidence to support a number of pleiotropic effects on the heart that may have the potential to influence cardiovascular outcomes. In this article, we review myocardial energy metabolism with particular emphasis on the potential benefits associated with a shift towards increased glucose utilisation and present the pre-clinical and clinical evidence regarding incretin effects on the heart. In addition we discuss the potential mechanism of action and benefit of drugs that modulate GLP-1 in patients with type 2 diabetes mellitus and coronary artery disease.

Keywords: Cardioprotection, diabetes, dipeptidyl peptidase-4, glucagon-like peptide-1, glucose, heart failure, incretin, ischaemia-reperfusion, metabolic modulation, myocardial metabolism