title: Incretin-based therapies in the management of type 2 diabetes: rationale and reality in a managed care setting.
abstract: In addition to the hypoglycemia and weight gain associated with many treatments for type 2 diabetes, alpha-glucosidase inhibitors, thiazolidinediones, metformin, sulfonylureas, and the glinides do not address all of the multiple defects existing in the pathophysiology of the disease. Cumulatively, these oral agents address the influx of glucose from the gastrointestinal tract, impaired insulin activity, and acute beta-cell dysfunction in type 2 diabetes; however, until recently, there were no means to deal with the inappropriate hyperglucagonemia or chronic beta-cell-decline characteristic of the disease. The recently introduced incretin-based therapies serve to address some of the challenges associated with traditionally available oral antidiabetic agents. In addition to improving beta-cell function, stimulating insulin secretion, and inhibiting glucagon secretion, these agents reduce appetite, thereby stabilizing weight and/or promoting weight loss in patients with type 2 diabetes. Of the incretin-based therapies, both the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and inhibit glucagon secretion. The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 receptor agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and saxagliptin. Earlier and more frequent use of these incretin-based therapies is recommended in the treatment of type 2 diabetes, based on their overall safety and ability to achieve the glycosylated hemoglobin level goal. As such, both the American Diabetes Association and the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) treatment algorithms recommend the use of incretin-based therapy in both treatment-naive and previously treated patients. The AACE/ACE guidelines clearly state that these agents should not be limited to third- or fourth-line therapy.
authors.affiliation: Division of Diabetes, Endocrinology, & Metabolism, Baylor College of Medicine, Ste 1000, Houston, TX 77030, USA. agarber@bcm.edu
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Garber
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000191:economics / Q000627:therapeutic use; D000465:Algorithms; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000191:economics; D004151:Dipeptides / Q000191:economics / Q000627:therapeutic use; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000191:economics / Q000627:therapeutic use*; D019317:Evidence-Based Medicine; D000077270:Exenatide; D005934:Glucagon / Q000187:drug effects / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D006801:Humans; D007004:Hypoglycemic Agents / Q000191:economics / Q000627:therapeutic use*; D054795:Incretins / Q000191:economics / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D000069450:Liraglutide; D008329:Managed Care Programs / Q000191:economics* / Q000706:statistics & numerical data; D010455:Peptides / Q000191:economics / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use; D014688:Venoms / Q000191:economics / Q000627:therapeutic use
chemical_list: D000218:Adamantane; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000077270:Exenatide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D000069450:Liraglutide; D010455:Peptides; D011719:Pyrazines; D018027:Receptors, Glucagon; D000068900:Sitagliptin Phosphate; D014230:Triazoles; D014688:Venoms; C000593833:GLP1R protein, human; C502994:saxagliptin