GLP-1 receptor agonists: A clinical perspective on cardiovascular effects

Abstract

The active incretin hormone glucagon-like peptide-1(7-36)amide (GLP-1) is a 30-amino acid peptide that exerts glucoregulatory and insulinotropic actions by functioning as an agonist for the GLP-1 receptor (GLP-1R). In addition to its anti-diabetic effects, GLP-1 has demonstrated cardioprotective actions. Here we review the cardiovascular effects of the GLP-1 analogues currently approved for the treatment of type 2 diabetes, namely exenatide and liraglutide. We discuss their anti-hyperglycaemic efficacy, and offer a clinical perspective of their effects on cardiovascular risk factors such as body weight, blood pressure, heart rate and lipid profiles, as well as their potential consequences on cardiovascular events, such as arrhythmias, heart failure, myocardial infarction and death. Lastly, we briefly review additional GLP-1R agonists in clinical development.

Glucagon-like peptide-1 receptor activation reverses cardiac remodeling via normalizing cardiac steatosis and oxidative stress in type 2 diabetes

“…In addition to its therapeutic action on diabetic condition, accumulating evidence demonstrated that GLP-1R agonism ameliorates systolic dysfunction in preclinical (2,22) and clinical heart failure after ischemic heart disease (3,20). Furthermore, recent reports have demonstrated the GLP-1 analog liraglutide ameliorates liver (19) and cardiac steatosis via modulation on the endoplasmic reticulum (ER) stress (24) in diet-induced obesity (DIO) mice.…”

In Vitro Metabolism of the Glucagon-Like Peptide-1 (GLP-1)–Derived Metabolites GLP-1(9-36)amide and GLP-1(28-36)amide in Mouse and Human Hepatocytes

“…The glucoincretin hormone glucagon-like peptide-1 (GLP-1) is derived from a proglucagon precursor and secreted by intestinal enteroendocrine L cells in response to oral nutrient ingestion (Kieffer and Habener, 1999;Holst, 2007;Lovshin and Drucker, 2009;Mundil et al, 2012). The majority of circulating GLP-1 levels comprise the 30-amino acid peptide GLP-1(7-36)amide, which acts through a seventransmembrane-spanning, heterotrimeric class B G protein-coupled receptor on pancreatic b cells to exert glucoregulatory and insulinotropic actions (Thorens, 1992).…”

Targeting composite treatment of type 2 diabetes in middle-income countries – walking a tightrope between hyperglycaemia and the dangers of hypoglycaemia

“…[1] Some of these new therapeutic agents, the incretins, have been shown to lower traditional cardiovascular risk factors and also mitigate newly identified risk factors such as hypoglycaemia and weight gain, both of which often develop as adverse effects when tight glucose control is achieved. [2] The WHO Multinational Study of Vascular Disease in Diabetes showed that 52% of deaths in T2DM are attributed to cardiovascular disease. [3] Addressing both traditional and emerging cardiovascular risk factors by utilising a more composite glucose-lowering strategy may more readily achieve a comprehensive reduction in cardiovascular risk factors and a meaningful reduction in cardiovascular mortality.…”