title: Clinical effects of once-weekly exenatide for the treatment of type 2 diabetes mellitus.
abstract: OBJECTIVE
  The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, administration, dosage, place in therapy, and cost of extended-release exenatide are reviewed.
  
  
  CONCLUSIONS
  Regular-release exenatide has a half-life of 2.4 hours and is administered twice daily. In order to allow for once-weekly administration, exenatide was encapsulated in poly(lactic-co-glycolic acid) microspheres, a biodegradable polymer. After subcutaneous injection, the microspheres slowly degrade, and the drug is released. A single injection of extended-release exenatide reaches maximum plasma concentration after 4-8 hours and remains at therapeutic levels for 8-16 hours, depending on the dosage. Based on the pharmacokinetics of a single dose, researchers determined that 0.8- and 2-mg once-weekly doses were likely to maintain therapeutic levels in the serum. Patients who used extended-release exenatide monotherapy had significantly lower glycosylated hemoglobin (HbA1c) levels and lost more weight than those receiving sitagliptin or pioglitazone (p < 0.05). In combination with metformin, extended-release exenatide reduced HbA1c levels more than did insulin glargine. This new formulation reduced HbA1c levels by 1.5-1.9%, fasting blood glucose concentrations by 31-42 mg/dL, and weight by 2.3-3.7 kg. The most common adverse events were injection-site reactions and transient nausea. Postmarketing reports have described acute pancreatitis and acute necrotizing or hemorrhagic pancreatitis in patients treated with exenatide. The published average wholesale price for a one-month supply of extended-release exenatide 2 mg is $388.
  
  
  CONCLUSIONS
  Extended-release exenatide taken once weekly is an effective second-line therapy for patients with type 2 diabetes who have not achieved glycemic goals with metformin alone.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, Mercer University, DuVall 148, 3001 Mercer University Drive, Atlanta, GA 30341, USA. ryan_gj@mercer.edu
authors.forename: Gina J
authors.initials: GJ
authors.lastname: Ryan
authors.forename: Nader H
authors.initials: NH
authors.lastname: Moniri
authors.forename: Dawn D
authors.initials: DD
authors.lastname: Smiley
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003692:Delayed-Action Preparations / Q000191:economics / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D016527:Drug Costs; D004359:Drug Therapy, Combination; D019317:Evidence-Based Medicine; D000077270:Exenatide; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D007279:Injections, Subcutaneous; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000627:therapeutic use; D008687:Metformin / Q000627:therapeutic use; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D000077205:Pioglitazone; D011719:Pyrazines / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D003692:Delayed-Action Preparations; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008687:Metformin; D010455:Peptides; D000077205:Pioglitazone; D011719:Pyrazines; D000068900:Sitagliptin Phosphate; D045162:Thiazolidinediones; D014230:Triazoles; D014688:Venoms