title: Exenatide: an incretin mimetic for the treatment of type 2 diabetes mellitus.
abstract: BACKGROUND
  Exenatide is a subcutaneously injected incretin mimetic. It is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus (T2DM) who are already receiving therapy with metformin, a sulfonylurea, or both but continue to have suboptimal glycemic control.
  
  
  OBJECTIVE
  This article reviews available information on the clinical pharmacology, comparative efficacy, tolerability, drug interactions, contraindications and precautions, dosage and administration, availability and storage, and cost of exenatide.
  
  
  METHODS
  MEDLINE (1966-April 2006) and Web of Science (1995-April 2006) were searched for original research and review articles published in the English language. The search terms used were exenatide, exendin-4, glucagon-Like peptide-1, GLP-1, and incretin mimetic. The reference lists of identified articles were also consulted, as was selected information from the package insert for exenatide. All relevant comparative efficacy studies that were available in published form were included in the review.
  
  
  RESULTS
  Naturally occurring incretins, such as glucagon-like peptide-1 (GLP-1), exhibit insulinotropic properties after release into the circulation from the gut. As a GLP-1 agonist, exenatide improves glucose homeostasis by mimicking the actions of naturally occurring GLP-1. It improves glycemic control by reducing fasting and postprandial glucose concentrations through a combination of known mechanisms, including glucose-dependent insulin secretion, restoration of first-phase insulin response, regulation of glucagon secretion, delaying gastric emptying, and decreasing food intake. Three Phase III comparative efficacy trials were identified that enrolled a total of 1,446 patients who received exenatide 5 pg SC BID, exenatide 10 mug SC BID, or placebo for 30 weeks in addition to their existing therapy with metformin, sulfonylurea, or both. In these trials, the addition of exenatide was associated with significant reductions in glycosylated hemoglobin (HbA(1c)) values (P < 0.001-P < 0.002), greater proportions of patients achieving an HbA(1c) <or=7%, significant decreases in fasting plasma glucose concentrations (P < 0.001-P < 0.005), and a dose-dependent progressive weight loss compared with placebo. Nausea (43.5%) was the most commonly reported adverse event in the combined exenatide groups. Other adverse events occurring in >10% of patients receiving exenatide were hypoglycemia (19.6%), diarrhea (12.8%), and vomiting (12.8%).
  
  
  CONCLUSIONS
  During clinical trials, exenatide added to existing metformin and/or sulfonylurea therapy in patients with T2DM reduced fasting and postprandial glucose concentrations, with improvements in HbA(1c) and modest weight loss. The main adverse effect associated with exenatide therapy was nausea.
authors.affiliation: Department of Pharmacotherapy, College of Pharmacy, Washington State University, Spokane, 99210-1495, USA. iltzj@wsu.edu
authors.forename: Jason L
authors.initials: JL
authors.lastname: Iltz
authors.forename: Danial E
authors.initials: DE
authors.lastname: Baker
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Setter
authors.forename: R
authors.initials: R
authors.lastname: Keith Campbell
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D000077270:Exenatide; D005215:Fasting; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use*; D010455:Peptides / Q000494:pharmacology*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D010455:Peptides; D013453:Sulfonylurea Compounds; D014688:Venoms