Incretin-based therapies: can we achieve glycemic control and cardioprotection?
Glucagon-like (GLP-1) is a peptide hormone secreted from the small intestine in response to nutrient ingestion. GLP-1 stimulates insulin secretion in a glucose-dependent manner, inhibits glucagon secretion and gastric emptying, and reduces appetite. Because of the short circulating half-life of the native GLP-1, novel GLP-1 receptor (GLP-1R) agonists and analogs and dipeptidyl peptidase 4 (DPP-4) inhibitors have been developed to facilitate clinical use. Emerging evidence indicates that GLP-1-based therapies are safe and may provide cardiovascular (CV) benefits beyond glycemic control. Preclinical and clinical studies are providing increasing evidence that GLP-1 therapies may positively affect CV function and metabolism by salutary effects on CV risk factors as well as via direct cardioprotective actions. However, the mechanisms whereby the various classes of incretin-based therapies exert CV effects may be mechanistically distinct and may not necessarily lead to similar CV outcomes. In this review, we will discuss the potential mechanisms and current understanding of CV benefits of native GLP-1, GLP-1R agonists and analogs, and of DPP-4 inhibitor therapies as a means to compare their putative CV benefits.
Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Hospital of the University of Pennsylvania, 3400 Spruce Street, Centrex 100, Philadelphia, Pennsylvania 19104, USA.
Franca S
FS
Angeli
Richard P
RP
Shannon
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000627:therapeutic use*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D054795:Incretins; D052216:Glucagon-Like Peptide 1
cardioprotection; dipeptidyl peptidase 4; glucagon-like peptide 1; incretins; type 2 diabetes mellitus