Incretin-Based Therapy for the Management of Type 2 Diabetes

Incretin-based therapy comprises dipeptidyl peptidase-4 inhibitors (DPP-4i) which raise concentrations of endogenous incretin hormones or glucagon-like peptide-1 (GLP-1) receptor agonists which activate the endogenous GLP-1 receptor. Several hypotheses have been proposed regarding the mechanisms for these diminished incretin effects, as well as the role of incretins in development of diabetes. Multiple other GLP-1 receptor agonists (RAs) have been approved for use in type 2 diabetes. Semaglutide is the newest GLP-1 RA to be FDA-approved for use in type 2 diabetes. Endogenous DPP-4 functions to degrade GLP-1, reducing its biological half-life. Diabetes confers significant morbidity and mortality, with atherosclerotic cardiovascular disease being the leading cause of death among those affected. The emergence of randomized controlled trials dramatically transformed the landscape of diabetes management and opened the door to novel therapies portending both glycemic and cardiovascular benefit. The incretin effect mediates insulin release and glucagon suppression in response to meal ingestion.