Incretin-based therapies: review of current clinical trial data.
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.
Peters
Anne
A
Clinical Diabetes Programs, University of Southern California, Los Angeles, California, USA. momofmax@mac.com
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
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