Angioedema associated with dipeptidyl peptidase-IV inhibitors

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

doi:10.1186/s12948-021-00164-7

Angioedema associated with dipeptidyl peptidase-IV inhibitors

Clin Mol Allergy. 2021 Dec 6;19(1):24. doi: 10.1186/s12948-021-00164-7.

Authors

Nicoletta Cassano¹, Eustachio Nettis², Elisabetta Di Leo³, Francesca Ambrogio⁴, Gino A Vena¹, Caterina Foti⁴

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. elisabettadileo71@libero.it.
⁴ Unit of Dermatology, Department of Biomedical Science and Human Oncology, University of Bari "Aldo Moro", Bari, Italy.

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.

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

Publication types

Review