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exenatide (Byetta, AC2993, extendin-4, Gilly, Lizzie, Bydureon)

Originally isolated from the saliva of Gila monsters* Patients may call it 'Gilly' or 'Lizzie' Indications: - diabetes mellitus type 2 - for use in conjunction with - metformin &/or sulfonylurea - insulin [12]; Insulin Glargine (Lantus) [13] - somewhat improves glycemic control in an inpatient setting [22] - may have symptomatic benefit in Parkinson's disease [20] Contraindications: - once weekly SQ exenatide does not diminish risk of cardiovascular events [21] - gastroparesis [23] Dosage: - 2.5-10 ug injection SC BID - Bydureon, once weekly long-acting form [8,15,19] - FDA-approved Jan 2012 - once weekly Bydureon as effective as metformin in decreasing hemoglobin A1c & in weight reduction [16] - promotes weight reduction in patients with or without diabetes mellitus [17] Byetta pens can be kept at room temperature for 30 days Adverse effects: - nausea/vomiting (frequent, but tends to lessen with time) [3] - acute pancreatitis (hemorrhagic, necrotizing) [6,7] - does not increase risk of acute pancreatis [11] - acute renal failure (risk 1 in 13,000) [9] Mechanism of action: 1) incretin mimetic 2) stimulation of the glucagon-like peptide-1 receptor 3) stimulation of insulin production in response to high blood glucose levels 4) inhibition of the release of glucagon 5) slowing the rate of gastric emptying 6) appetite suppression 7) preservation & formation of pancreatic beta cells 8) weight loss [14] * The Gila monster eats four times a year, & at these times, exendin-4 is released to turn the pancreas on. Notes: - exenatide is associated with less hypoglycemia lower body weight (4.5-kg difference) than insulin glargine - HbA1c effects are similar to insulin glargine Estimated cost (2005) = $200/month; $323.month (2011)

Interactions

drug interactions drug adverse effects (more general classes)

General

glucagon-like peptide 1 (GLP-1) receptor agonist; incretin mimetic; GLP-1 mimetic; GLP-1 agonist; glutide; GLP-1RA peptide

References

  1. Prescriber's Letter 11(7):41 2004 Exenatide (Synthetic Exendin-4) Detail-Document#: 200705 (subscription needed) http://www.prescribersletter.com
  2. Journal Watch 25(12):100, 2005 DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005 May;28(5):1092-100. PMID: 15855572 - Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005 May;28(5):1083-91. PMID: 15855571 - Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD; Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004 Nov;27(11):2628-35. PMID: 15504997 http://care.diabetesjournals.org/cgi/content/full/27/11/2628
  3. Heine RJ, Van Gaal LF, Johns D, Mihm MJ, Widel MH, Brodows RG; GWAA Study Group. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2005 Oct 18;143(8):559-69. Summary for patients in: Ann Intern Med. 2005 Oct 18;143(8):I30. PMID: 16230722
  4. Prescriber's Letter 13(5): 2006 Byetta (Exenatide) for Weight Loss Detail-Document#: 220506 (subscription needed) http://www.prescribersletter.com
  5. Prescriber's Letter 14(4): 2007 Change in storage for Byetta and new insulin pens: HumaPen Memoir and HumaPen Luxura HD Detail-Document#: 230408 (subscription needed) http://www.prescribersletter.com
  6. FDA Medwatch http://www.fda.gov/medwatch/safety/2007/safety07.htm#Byetta http://www.fda.gov/CDER/Drug/InfoSheets/HCP/exenatide2008HCP.htm - Prescriber's Letter 14(11): 2007 Pancreatitis and Byetta (Exenatide) Detail-Document#: 231104 (subscription needed) http://www.prescribersletter.com
  7. FDA MedWatch http://www.fda.gov/medwatch/safety/2007/safety07.htm#Byetta
  8. Drucker DJ et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: A randomised, open-label, non-inferiority study. Lancet 2008 Oct 4; 372:1240 PMID: 18782641
  9. FDA NEWS RELEASE, Nov. 2, 2009 Byetta Label Revised to Include Safety Information on Possible Kidney Problems http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm188708.htm - Prescriber's Letter 16(12): 2009 Byetta (Exenatide) and Altered Kidney Function Detail-Document#: 251203 (subscription needed) http://www.prescribersletter.com
  10. Diamant M et al Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial The Lancet 2010, 375(9733):2234-2243 PMID: 20609969 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60406-0/fulltext
  11. Garg R et al. Acute pancreatitis in type 2 diabetes treated with exenatide or sitagliptin: A retrospective observational pharmacy claims analysis. Diabetes Care 2010 Nov; 33:2349. PMID: 20682680 - Gonzalez-Perez A et al. Acute pancreatitis in association with type 2 diabetes and antidiabetic drugs: A population-based cohort study. Diabetes Care 2010 Dec; 33:2580. PMID: 20833867
  12. Buse JB et al. Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: A randomized, controlled trial. Ann Intern Med 2011 Jan 18; 154:103 PMID: 21138825 - Nathan DM. Time for clinically relevant comparative effectiveness studies in type 2 diabetes. Ann Intern Med 2011 Jan 18; 154:131 PMID: 21135287
  13. Prescriber's Letter 18(12): 2011 Using Exenatide (Byetta) with Insulin Glargine (Lantus) Detail-Document#: 271204 (subscription needed) http://www.prescribersletter.com
  14. Vilsbol T Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials BMJ 2012;344:d7771 PMID: 22236411 http://www.bmj.com/node/557082 - Padwal R Glucagon-like peptide-1 agonists BMJ 2012;344:d7282 PMID: 22236410 http://www.bmj.com//node/557081
  15. FDA Approves BYDUREON - The First and Only Once-Weekly Treatment for Type 2 Diabetes http://phx.corporate-ir.net/phoenix.zhtml?c=101911&p=irol-newsArticle&ID=1653756
  16. Russell-Jones D et al. Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug- naive patients with type 2 diabetes (DURATION-4): A 26-week double-blind study. Diabetes Care 2012 Feb; 35:252. PMID: 22210563
  17. Vilsboll T et al. Effects of glucagon-like peptide-1 receptor agonists on weight loss: Systematic review and meta-analyses of randomised controlled trials. BMJ 2012 Jan 11; 344:d7771. PMID: 22236411
  18. Diamant M et al. Safety and efficacy of once-weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes over 84 weeks. Diabetes Care 2012 Apr; 35:683 PMID: 22357185
  19. Buse JB et al Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): A randomised, open-label study. Lancet 2012 Nov 7 PMID: 23141817 http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61267-7/fulltext
  20. Athauda D, Maclagan K, Skene SS et al. Exenatide once weekly versus placebo in Parkinson's disease: A randomised, double-blind, placebo-controlled trial. Lancet 2017 Aug 3 PMID: 28781108
  21. Holman RR, Bethel MA, Mentz RJ et la Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2017 Sep 28; 377:1228. PMID: 28910237 http://www.nejm.org/doi/full/10.1056/NEJMoa1612917
  22. Fayfman M, Galindo RJ, Rubin DJ et al. A randomized controlled trial on the safety and efficacy of exenatide therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes. Diabetes Care 2019 Mar; 42:450-456 PMID: 30679302 http://care.diabetesjournals.org/content/42/3/450
  23. NEJM Knowledge+ Endocrinology