title: Differentiating incretin-based therapies for population-based health care.
abstract: Incretin hormones, such as glucagon-like peptide-1 (GLP-1), play a crucial role in modulating insulin and glucagon secretion, as well as regulating appetite, gastric emptying, and pancreatic beta cell function. The pathophysiology of type 2 diabetes mellitus (T2DM) is complex and includes impaired incretin response, among other metabolic abnormalities. Incretin-based treatments for T2DM, such as GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, mimic or prolong the actions of incretin hormones and function in a glucose-dependent manner, thereby reducing hyperglycemia and avoiding hypoglycemia. There are important mechanistic differences between the GLP-1 receptor agonists and the DPP-4 inhibitors. DPP-4 inhibitors protect endogenous GLP-1 from DPP-4 degradation, thereby achieving a physiologic level of GLP-1. In contrast, GLP-1 receptor agonists act directly on the GLP-1 receptor, achieving a pharmacologic level of GLP-1 activity. These different mechanisms yield different effects on diabetes and weight loss. Incretin-based treatments may improve beta cell function, and, while not indicated for these effects, GLP-1 receptor agonists may also promote satiety, reduce weight, slow gastric emptying, and possibly improve hypertension and triglyceride levels; these characteristics are absent with DPP-4 inhibitors. Therefore, GLP-1 receptor agonists can be an appropriate clinical choice for glycemic control in patients with T2DM, especially in those who would benefit from weight loss or are prone to hypoglycemia.
authors.affiliation: MedMetrics Health Partners, 100 Century Dr, Worcester, MA 01606, USA. calabreseds@charter.net
authors.forename: Dave
authors.initials: D
authors.lastname: Calabrese
mesh_terms: D001786:Blood Glucose / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects; D002985:Clinical Protocols; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism / Q000627:therapeutic use; D004361:Drug Tolerance; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists / Q000627:therapeutic use; D015431:Weight Loss / Q000187:drug effects
chemical_list: D001786:Blood Glucose; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D018027:Receptors, Glucagon; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4