title: Incretin-based therapies: review of current clinical trial data.
abstract: Incretin hormones are secreted in response to food ingestion and help manage glycemic control by regulating insulin and glucagon release, slowing gastric emptying, and reducing caloric intake. Glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, secreted from the L-cells of the lower gut and K-cells of the intestines, respectively, are responsible for these incretin effects, which are reduced in patients with type 2 diabetes mellitus. Initially, the rapid degradation of either incretin by dipeptidyl peptidase-4 (DPP-4) complicated the development of viable therapeutics based on either hormone. However, the US Food and Drug Administration (FDA) has approved 2 incretin-based therapies in which their mechanisms of action augment or amplify the effects of naturally occurring GLP-1. Exenatide, a first-in-class GLP-1 receptor agonist, exhibits the same mechanisms of action as native GLP-1. Sitagliptin inhibits the DPP-4 enzyme, thus increasing the half-life of endogenous GLP-1. This review examines data from recent GLP-1 receptor agonist and DPP-4 inhibitor studies in patients with type 2 diabetes, as well as data on other incretin-based therapies in clinical development.
authors.affiliation: Clinical Diabetes Programs, University of Southern California, Los Angeles, California, USA. momofmax@mac.com
authors.forename: Anne
authors.initials: A
authors.lastname: Peters
mesh_terms: D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D010455:Peptides / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use; D014688:Venoms / Q000627:therapeutic use
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D054795:Incretins; D010455:Peptides; D011719:Pyrazines; D018027:Receptors, Glucagon; D014230:Triazoles; D014688:Venoms; D000077270:Exenatide; D000068900:Sitagliptin Phosphate