Effects of glucagon-like peptide-1 and long-acting analogues on cardiovascular and metabolic function

Although the insulinotropic role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus has been substantiated, its role in cardioprotection remains largely unknown. To ascertain the role of the cardiovascular actions of GLP-1 in health and disease states necessitates a review of the current evidence as well as ongoing investigation. Of cardiovascular significance, both positive inotropic and chronotropic effects, unmodifiable by beta-adrenergic blockers, have been reportedly attributed to GLP-1 actions on the myocardium. However, the potent role of GLP-1 and its analogues in eliciting tachycardic and pressor effects should be of some concern. Aside from its reported insulinotropic activity, GLP-1 impacts the myocardium directly. Highly specific GLP-1 receptors have been identified in the heart and within the central nervous system, particularly in the nucleus tractus solitarius, a neuromodulatory centre of cardiovascular control. The occurrence of GLP-1 receptors in cardiac tissue and autonomic regions of cardiovascular control has stimulated investigation, particularly as these sites may be suitable targets for the pharmacological action of GLP-1 and long-acting analogues. Discordance on the haemodynamic consequences of GLP-1 pharmacotherapy in experimental animals and human patients has been reported in the literature. However, long-term pharmacological doses of GLP-1 have shown prolonged and beneficial actions on cardiovascular homeostasis in the adjuvant treatment of metabolic disease.