Display options
Share it on

Clin Mol Allergy. 2021 Dec 06;19(1):24. doi: 10.1186/s12948-021-00164-7.

Angioedema associated with dipeptidyl peptidase-IV inhibitors.

Clinical and molecular allergy : CMA

Nicoletta Cassano, Eustachio Nettis, Elisabetta Di Leo, Francesca Ambrogio, Gino A Vena, Caterina Foti

Affiliations

  1. Dermatology and Venereology Private Practice, Bari and Barletta, Italy.
  2. Department of Emergency and Organ Transplantation, School and Chair of Allergy and Clinical Immunology, University of Bari "Aldo Moro", Bari, Italy.
  3. Section of Allergy and Clinical Immunology, Unit of Internal Medicine, "F. Miulli" Hospital, Strada Provinciale per Santeramo Km 4.100, Acquaviva delle Fonti, Bari, Italy. [email protected].
  4. Unit of Dermatology, Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy.

PMID: 34872575 PMCID: PMC8647342 DOI: 10.1186/s12948-021-00164-7

Abstract

BACKGROUND: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, also known as gliptins, are a class of oral antidiabetic agents. Postmarketing reports have documented the occurrence of angioedema in patients treated with gliptins and it was found that these drugs increased the risk of angioedema in patients concurrently treated with angiotensin-converting enzyme inhibitors (ACEIs). The aim of this manuscript is to provide an overview of the risk of angioedema associated with gliptins.

METHODS: The keywords used for the literature search in the PubMed database included "angioedema" and "dipeptidyl peptidase", "gliptins", or the name of each DPP-IV inhibitor. Articles in English published up to December 2020 were taken into consideration.

RESULTS: The available data appear to rule out a higher risk of angioedema associated with gliptin monotherapy and have revealed an increased susceptibility in patients simultaneously treated with gliptins and ACEIs. However, one single multicenter phase IV trial and case reports, even if very limited in number, have shown that angioedema can also occur during treatment with DPP-IV inhibitors without the concomitant use of ACEIs. The involvement of other drugs and drug interactions has occasionally been suggested. In a few patients, deficiency of enzymes involved in bradykinin catabolism was detected and this finding can constitute a risk factor for angioedema exacerbated by treatment with DPP-IV inhibitors.

CONCLUSIONS: This risk of angioedema associated with the use of gliptins has mostly been related to the concurrent administration of ACEIs, and has been considered rare, but it might be underestimated and underreported. The role of additional risk factors or drug interactions deserves further investigations. Caution should be taken when considering the use of DPP-IV inhibitors in patients treated with ACEIs or presenting with other known risk factors for angioedema.

© 2021. The Author(s).

Keywords: Angioedema; Angiotensin-converting enzyme inhibitors; Bradykinin; Dipeptidyl peptidase-IV inhibitors; Gliptins

References

  1. Diabetes Care. 2011 May;34 Suppl 2:S276-8 - PubMed
  2. J Allergy Clin Immunol Pract. 2017 May - Jun;5(3):744-749 - PubMed
  3. Diabetes Metab Res Rev. 2014 Oct;30(7):556-69 - PubMed
  4. J Community Hosp Intern Med Perspect. 2019 Dec 14;9(6):453-459 - PubMed
  5. Br J Anaesth. 2012 Nov;109(5):827-9 - PubMed
  6. Br J Clin Pharmacol. 2016 Dec;82(6):1647-1659 - PubMed
  7. Ann Allergy Asthma Immunol. 2008 Apr;100(4):327-32 - PubMed
  8. Arch Intern Med. 2005 Jul 25;165(14):1637-42 - PubMed
  9. Int J Cardiol. 2013 Oct 3;168(3):e106 - PubMed
  10. Aust Fam Physician. 2013 Dec;42(12):863-6 - PubMed
  11. Endocrinol Diabetes Metab. 2019 Jun 21;2(3):e00084 - PubMed
  12. Hypertension. 2008 Jun;51(6):1624-30 - PubMed
  13. J Allergy Clin Immunol Pract. 2019 Jul - Aug;7(6):2068-2069 - PubMed
  14. Immunol Allergy Clin North Am. 2017 Aug;37(3):483-495 - PubMed
  15. Hypertension. 2009 Sep;54(3):468-70 - PubMed
  16. J Allergy Clin Immunol. 2007 Aug;120(2):403-8 - PubMed
  17. Curr Hypertens Rep. 2018 Jun 8;20(7):55 - PubMed
  18. BMJ Case Rep. 2017 Jan 10;2017: - PubMed
  19. Eur Ann Allergy Clin Immunol. 2014 May;46(3):119-22 - PubMed
  20. Expert Opin Drug Saf. 2018 Apr;17(4):387-405 - PubMed
  21. Ann Intern Med. 2017 Jul 18;167(2):142-143 - PubMed
  22. J Investig Allergol Clin Immunol. 2020;30(4):272-280 - PubMed
  23. Curr Opin Allergy Clin Immunol. 2013 Aug;13(4):337-44 - PubMed
  24. N Engl J Med. 2013 Oct 3;369(14):1317-26 - PubMed
  25. Hypertension. 2008 Jan;51(1):141-7 - PubMed
  26. BMC Endocr Disord. 2010 Apr 22;10:7 - PubMed
  27. Allergy. 2010 Nov;65(11):1381-7 - PubMed
  28. Am J Case Rep. 2017 May 25;18:576-579 - PubMed
  29. J Allergy Clin Immunol Pract. 2020 Jul - Aug;8(7):2406-2408.e1 - PubMed
  30. Best Pract Res Clin Endocrinol Metab. 2009 Aug;23(4):479-86 - PubMed
  31. Am Heart J. 2011 Oct;162(4):620-626.e1 - PubMed
  32. Peptides. 1996;17(8):1397-403 - PubMed
  33. Hypertension. 2009 Sep;54(3):516-23 - PubMed
  34. BMC Endocr Disord. 2008 Oct 27;8:14 - PubMed
  35. J Allergy Clin Immunol Pract. 2017 May - Jun;5(3):610-615 - PubMed
  36. BMJ. 2006 May 20;332(7551):1177-81 - PubMed
  37. Ann Med. 2014 Dec;46(8):607-18 - PubMed
  38. Curr Diabetes Rev. 2018;14(4):327-333 - PubMed
  39. Int Immunopharmacol. 2020 Jan;78:106081 - PubMed
  40. Acta Cardiol. 2019 Aug;74(4):277-281 - PubMed
  41. Diabet Med. 2010 Apr;27(4):486-7 - PubMed
  42. Clin Pharmacol Ther. 1996 Jul;60(1):8-13 - PubMed
  43. Am J Cardiol. 2012 Aug 1;110(3):383-91 - PubMed
  44. J Eval Clin Pract. 2004 Nov;10(4):499-509 - PubMed
  45. Hypertension. 2002 Feb;39(2 Pt 2):460-4 - PubMed
  46. Am J Ther. 2020 Aug 03;: - PubMed
  47. Diabet Med. 2013 Apr;30(4):e149-50 - PubMed
  48. Diabetes Care. 2012 Aug;35(8):e60 - PubMed
  49. Orphanet J Rare Dis. 2018 May 4;13(1):73 - PubMed
  50. Nat Rev Endocrinol. 2020 Nov;16(11):642-653 - PubMed

Publication Types