Skip to main content
SpringerLink
Log in

Exenatide Extended-Release: An Updated Review of Its Use in Type 2 Diabetes Mellitus

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Exenatide extended-release (exenatide ER) [Bydureon®] is a glucagon-like peptide-1 receptor agonist, approved for the treatment of type 2 diabetes mellitus. It is injected subcutaneously by patients once weekly, with no dose titration required. This article updates an earlier review of exenatide ER in the management of type 2 diabetes, focusing on recently published data. In randomized, controlled trials, adjunctive exenatide ER 2 mg once weekly for 24–30 weeks significantly improved glycaemic control and reduced bodyweight in patients with inadequately controlled type 2 diabetes despite diet plus exercise and/or oral antihyperglycaemic drugs (OADs). These beneficial effects of exenatide ER were maintained after up to 6 years of treatment. In patients receiving one or more OADs, addition of exenatide ER provided better glycaemic control than an immediate-release formulation of exenatide (exenatide twice daily), sitagliptin, pioglitazone, insulin glargine or insulin detemir, and was slightly less effective than liraglutide. In patients treated with diet plus exercise alone, adjunctive exenatide ER was noninferior to metformin and superior to sitagliptin, but was not noninferior to pioglitazone. Exenatide ER was generally well tolerated, with a low inherent risk of hypoglycaemia. The most common adverse events were mild to moderate gastrointestinal events, injection-site reactions and headache. Thus, exenatide ER is a useful treatment option in the management of type 2 diabetes. It offers a convenient, once-weekly regimen and can be administered by patients via a pen injection system or syringes and needles.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140–9.

    Article  PubMed  Google Scholar 

  2. American Diabetes Association. Standards of medical care in diabetes: 2014. Diabetes Care. 2014;37(Suppl 1):S14–80.

    Article  Google Scholar 

  3. Garber AJ, Abrahamson MJ, Barzilay JI, et al. AACE comprehensive diabetes management algorithm. Endocr Pract. 2013;19(2):327–36.

    Article  PubMed  Google Scholar 

  4. Nauck MA. Unraveling the science of incretin biology. Am J Med. 2009;122(6 Suppl):S3–10.

    Article  PubMed  Google Scholar 

  5. McCormack PL. Exenatide twice daily: a review of its use in the management of patients with type 2 diabetes mellitus. Drugs. 2014;74(3):325–51.

    Article  CAS  PubMed  Google Scholar 

  6. DeYoung MB, MacConell L, Sarin V, et al. Encapsulation of exenatide in poly-(D, L-lactide-co-glycolide) microspheres produced an investigational long-acting once-weekly formulation for type 2 diabetes. Diabetes Technol Ther. 2011;13(11):1145–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. AstraZeneca. Bydureon® (exenatide extended-release for injectable suspension): US prescribing information. 2012. http://www.accessdata.fda.gov. Accessed 27 May 2015.

  8. LaRue S, Malloy J, Halili RB. Dual-chamber pen design and testing for injection of exenatide dispersed in poly-(D,L-lactide-co-glycolide) microspheres for once-weekly treatment of type 2 diabetes [abstract no. P-257]. In: 7th International Conference on Advanced Technology & Treatments for Diabetes. 2014.

  9. European Medicines Agency. Bydureon 2 mg powder and solvent for prolonged-release suspension for injection: summary of product characteristics. 2011. http://www.ema.europa.eu. Accessed 27 May 2015.

  10. AstraZeneca. US FDA approves Bydureon® Pen (exenatide extended-release for injectable suspension) for once-weekly treatment of adults with type 2 diabetes [media release]. 3 March 2014. http://www.astrazeneca.com.

  11. Scott LJ. Exenatide extended-release: a review of its use in type 2 diabetes mellitus. Drugs. 2012;72(12):1679–707.

    Article  CAS  PubMed  Google Scholar 

  12. Cvetkovic RS, Plosker GL. Exenatide: a review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea). Drugs. 2007;67(6):935–54.

    Article  CAS  PubMed  Google Scholar 

  13. Kim DM, Macconell LP, Zhuang DP, et al. Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care. 2007;30(6):1487–93.

    Article  CAS  PubMed  Google Scholar 

  14. Iwamoto K, Nasu R, Yamamura A, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of exenatide once weekly in Japanese patients with type 2 diabetes. Endocr J. 2009;56(8):951–62.

    Article  CAS  PubMed  Google Scholar 

  15. Ji L, Onishi Y, Ahn CW, et al. Efficacy and safety of exenatide once-weekly vs exenatide twice-daily in Asian patients with type 2 diabetes mellitus. J Diabetes Investig. 2013;4(1):53–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Inagaki N, Atsumi Y, Oura T, et al. Efficacy and safety profile of exenatide once weekly compared with insulin once daily in Japanese patients with type 2 diabetes treated with oral antidiabetes drug(s): results from a 26-week, randomized, open-label, parallel-group, multicenter, noninferiority study. Clin Ther. 2012;34(9):1892–908.

    Article  CAS  PubMed  Google Scholar 

  17. Russell-Jones D, Cuddihy RM, Hanefeld M, 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;35(2):252–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Diamant M, Van Gaal L, Stranks S, 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. Lancet. 2010;375(9733):2234–43.

    Article  CAS  PubMed  Google Scholar 

  19. Diamant M, Van Gaal L, Stranks S, 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;35(4):683–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Darpö B, Philip S, MacConell L, et al. Exenatide at therapeutic and supratherapeutic concentrations does not prolong the QTc interval in healthy subjects. Br J Clin Pharmacol. 2013;75(4):979–89.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Fineman M, Flanagan S, Taylor K, et al. Pharmacokinetics and pharmacodynamics of exenatide extended-release after single and multiple dosing. Clin Pharmacokinet. 2011;50(1):65–74.

    Article  CAS  PubMed  Google Scholar 

  22. Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008;372(9645):1240–50.

    Article  CAS  PubMed  Google Scholar 

  23. Cui YM, Guo XH, Zhang DM, et al. Pharmacokinetics, safety, and tolerability of single- and multiple-dose exenatide once weekly in Chinese patients with type 2 diabetes mellitus. J Diabetes. 2013;5(2):127–35.

    Article  CAS  PubMed  Google Scholar 

  24. Blevins T, Pullman J, Malloy J, et al. DURATION-5: exenatide once weekly resulted in greater improvements in glycemic control compared with exenatide twice daily in patients with type 2 diabetes. J Clin Endocrinol Metab. 2011;96(5):1301–10.

    Article  CAS  PubMed  Google Scholar 

  25. Buse JB, Nauck M, Forst T, et al. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a randomised, open-label study. Lancet. 2013;381(9861):117–24.

    Article  CAS  PubMed  Google Scholar 

  26. Bergenstal RM, Wysham C, MacConell L, et al. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010;376(9739):431–9.

    Article  PubMed  Google Scholar 

  27. Davies M, Heller S, Sreenan S, et al. Once-weekly exenatide versus once- or twice-daily insulin detemir. Diabetes Care. 2013;36(5):1368–76.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Diamant M, Van Gaal L, Guerci B, et al. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. Lancet Diabetes Endocrinol. 2014;2(6):464–73.

    Article  CAS  PubMed  Google Scholar 

  29. Macconell L, Pencek R, Li Y, et al. Exenatide once weekly: sustained improvement in glycemic control and cardiometabolic measures through 3 years. Diabetes Metab Syndr Obes. 2013;6:31–41.

    PubMed Central  PubMed  Google Scholar 

  30. Henry RR, Klein EJ, Malloy J, et al. DURATION-1 extension: efficacy and tolerability of exenatide once weekly (QW) over 6 years in patients with T2DM [abstract no. 964-P]. In: 74th Annual Scientific Sessions of the American Diabetes Association. 2014.

  31. Buse JB, Drucker DJ, Taylor KL, et al. DURATION-1: exenatide once weekly produces sustained glycemic control and weight loss over 52 weeks. Diabetes Care. 2010;33(6):1255–61.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Taylor K, Gurney K, Han J, et al. Exenatide once weekly treatment maintained improvements in glycemic control and weight loss over 2 years. BMC Endocr Disord. 2011;11:9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Wysham C, Bergenstal R, Malloy J, et al. DURATION-2: efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once-weekly exenatide. Diabet Med. 2011;28(6):705–14.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Wysham CH, MacConell LA, Maggs DG, et al. Five-year efficacy and safety data of exenatide once weekly: long-term results from the randomized, controlled DURATION-1 trial. Mayo Clin Proc. 2015;90(3):356–65.

    Article  CAS  PubMed  Google Scholar 

  35. Scott DA, Boye KS, Timlin L, et al. A network meta-analysis to compare glycaemic control in patients with type 2 diabetes treated with exenatide once weekly or liraglutide once daily in comparison with insulin glargine, exenatide twice daily or placebo. Diabetes Obes Metab. 2013;15(3):213–23.

    Article  CAS  PubMed  Google Scholar 

  36. Grimm M, Li Y, Brunell SC, et al. Exenatide once weekly versus daily basal insulin as add-on treatment to metformin with or without a sulfonylurea: a retrospective pooled analysis in patients with poor glycemic control. Postgrad Med. 2013;125(5):101–8.

    Article  PubMed  Google Scholar 

  37. Malloy J, Meloni A, Han J. Efficacy and tolerability of exenatide once weekly versus sitagliptin in patients with type 2 diabetes mellitus: a retrospective analysis of pooled clinical trial data. Postgrad Med. 2013;125(3):58–67.

    Article  PubMed  Google Scholar 

  38. Grimm M, Han J, Weaver C, et al. Efficacy, safety, and tolerability of exenatide once weekly in patients with type 2 diabetes mellitus: an integrated analysis of the DURATION trials. Postgrad Med. 2013;125(3):47–57.

    Article  PubMed  Google Scholar 

  39. Norwood P, Liutkus JF, Haber H, et al. Safety of exenatide once weekly in patients with type 2 diabetes mellitus treated with a thiazolidinedione alone or in combination with metformin for 2 years. Clin Ther. 2012;34(10):2082–90.

    Article  CAS  PubMed  Google Scholar 

  40. Blonde L, Macconell L, Huang W, et al. Exenatide once weekly: association between weight response, glycemic control, and markers of cardiovascular risk [abstract no. 1182-P]. Diabetes. 2013;62(Suppl 1):A308–9.

    Google Scholar 

  41. Chilton RJ, MacConell LA, Han JC, et al. Characterization of heart rate increases with glucagon-like peptide-1 agonist therapy [abstract no. A16290]. Circulation. 2013;128(Suppl 2).

  42. Best JH, Boye KS, Rubin RR, et al. Improved treatment satisfaction and weight-related quality of life with exenatide once weekly or twice daily. Diabet Med. 2009;26(7):722–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Best JH, Rubin RR, Peyrot M, et al. Weight-related quality of life, health utility, psychological well-being, and satisfaction with exenatide once weekly compared with sitagliptin or pioglitazone after 26 weeks of treatment. Diabetes Care. 2011;34(2):314–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  44. MacConell L, Gurney K, Malloy J, et al. Safety and tolerability of exenatide once weekly in patients with type 2 diabetes: an integrated analysis of 4,328 patients. Diabetes Metab Syndr Obes. 2015;8:241–53.

    PubMed Central  PubMed  Google Scholar 

  45. Ridge T, Moretto T, MacConell L, et al. Comparison of safety and tolerability with continuous (exenatide once weekly) or intermittent (exenatide twice daily) GLP-1 receptor agonism in patients with type 2 diabetes. Diabetes Obes Metab. 2012;14(12):1097–103.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Cirincione B, Edwards J, Aisporna M, et al. Gastrointestinal tolerability with twice-daily or once-weekly exenatide formulations was not predicted by concentration with long-term treatment [abstract no. 910]. Diabetologia. 2013;56(Suppl 1):S363.

    Google Scholar 

  47. Tuttle KR, Heilmann C, Hoogwerf BJ, et al. Effects of exenatide on kidney function, adverse events, and clinical end points of kidney disease in type 2 diabetes. Am J Kidney Dis. 2013;62(2):396–8.

    Article  CAS  PubMed  Google Scholar 

  48. Fineman MS, Mace KF, Diamant M, et al. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012;14(6):546–54.

    Article  CAS  PubMed  Google Scholar 

  49. Gaebler JA, Soto-Campos G, Alperin P, et al. Health and economic outcomes for exenatide once weekly, insulin, and pioglitazone therapies in the treatment of type 2 diabetes: a simulation analysis. Vasc Health Risk Manag. 2012;8(1):255–64.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. Guillermin AL, Lloyd A, Best JH, et al. Long-term cost-consequence analysis of exenatide once weekly vs sitagliptin or pioglitazone for the treatment of type 2 diabetes patients in the United States. J Med Econ. 2012;15(4):654–63.

    Article  PubMed  Google Scholar 

  51. Samyshkin Y, Guillermin AL, Best JH, et al. Long-term cost-utility analysis of exenatide once weekly versus insulin glargine for the treatment of type 2 diabetes patients in the US. J Med Econ. 2012;15(Suppl 2):6–13.

    Article  PubMed  Google Scholar 

  52. Fonseca T, Clegg J, Caputo G, et al. The cost-effectiveness of exenatide once weekly compared with exenatide twice daily and insulin glargine for the treatment of patients with type two diabetes and body mass index ≥30 kg/m2 in Spain. J Med Econ. 2013;16(7):926–38.

    Article  PubMed  Google Scholar 

  53. Johnston SS, Nguyen H, Felber E, et al. Retrospective study of adherence to glucagon-like peptide-1 receptor agonist therapy in patients with type 2 diabetes mellitus in the United States. Adv Ther. 2014;31(11):1119–33.

    Article  CAS  PubMed  Google Scholar 

Download references

Disclosure

The preparation of this review was not supported by any external funding. Yahiya Y. Syed and Paul L. McCormack are salaried employees of Adis/Springer. During the peer review process, the manufacturer of the agent under review was offered an opportunity to comment on this article. Changes resulting from comments received were made by the author(s) on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Yahiya Y. Syed & Paul L. McCormack

Authors
  1. Yahiya Y. Syed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul L. McCormack
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yahiya Y. Syed.

Additional information

The manuscript was reviewed by: P. Dandona, Department of Medicine, The University at Buffalo, Buffalo, NY, USA; G. Derosa, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy; A.D. Mooradian, Department of Medicine, University of Florida, Jacksonville, FL, USA.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Syed, Y.Y., McCormack, P.L. Exenatide Extended-Release: An Updated Review of Its Use in Type 2 Diabetes Mellitus. Drugs 75, 1141–1152 (2015). https://doi.org/10.1007/s40265-015-0420-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-015-0420-z

Keywords

Search

Navigation