An Overview of Incretin-Based Therapies: Pharmacology and Future Perspectives

Abstract

Glucagon-like peptide-1 (GLP-1) is a gut-derived incretin hormone that is released upon nutrient ingestion stimulating insulin secretion, suppressing glucagon secretion, and suppressing appetite and food intake which contribute to glucose homeostasis. The incretin system is impaired during type 2 diabetes mellitus (T2DM). Incretin-based therapies are gaining popularity in the clinical field nowadays. Current treatment guidelines for T2DM incorporate glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase 4 inhibitors (DPP-4i) as second-line agents with the advantages of low risk of hypoglycemia with good control of postprandial hyperglycemia (with short-acting GLP-1 RAs and DPP-4i) and weight loss (with GLP-1 RAs). GLP-1 RAs have more efficacy and are preferred with patients with preexisting cardiovascular disease. Growing evidence suggests that incretin-based therapies have beneficial effects on cardiovascular, liver, kidney, and nervous system disorders. The current review includes the biology of the incretin system, the pharmacology of incretinbased therapies, and their applications in experimental and clinical work.