{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:02:30Z","timestamp":1787029350395,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Bullous pemphigoid (BP) is an autoimmune blistering skin disease. The association between dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors) and bullous pemphigoid (BP) has been studied in many countries; however, controversy has arisen from analyzing the related risk factors. The objectives of this study are to assess whether the association between DPP-4 inhibitors and bullous pemphigoid in EudraVigilance is statistically significant and to identify the presence of risk factors found in previous studies in a case\/exposure group. Our results will be compared with those obtained from the Food and Drug Administration Adverse Event Reporting System database (FAERS). Methods: A case\/control retrospective observational study was performed using data from the European database EudraVigilance. All reports from 2007 to 2024 (a total of 11,451,738 reports) were gathered and filtered by exposure to DPP-4 inhibitors and development of BP or lack thereof. Association was measured using reporting odds ratios with a 95% confidence interval, and Fisher\u2019s exact test was used to obtain p-values, assuming an alpha error of 0.05. Results: The results indicate an association between the consumption of DPP-4 inhibitors and the development of BP (with an odds ratio of 153.5; 95% confidence interval 144.1\u2013163.5; ROR = (a\/c)\/(b\/d); a: 1345 reports of BP associated with DPP-4i; c: 3870 reports of BP associated with other different drugs; b: 25,857 reports of other ADRs and DPP-4i; and d: 11,420,666 reports of ADRs associated with other drugs). The predominant factors in the case\/exposure group were male gender (58.6%), age between 65 and 85 years (43.3%), medical history of type 2 diabetes mellitus (30.4%) and consumption of vildagliptin (44.2%). Similar results were found in a prior analysis of the FAERS database (2006\u20132020). Conclusions: This study provides evidence of the association between the consumption of gliptins and the development of BP. Disproportionality measures were estimated to be higher in the exposure group than in the positive controls. As such, BP could appear after several months of exposure, and dermatological monitoring is crucial.<\/jats:p>","DOI":"10.3390\/ph18121800","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:04:57Z","timestamp":1764151497000},"page":"1800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association Between DPPs-4 Inhibitors and Bullous Pemphigoid: Reporting Odds Ratio Analysis Using EudraVigilance Database"],"prefix":"10.3390","volume":"18","author":[{"given":"Alex Carbonell","family":"Pedrero","sequence":"first","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Pompeu Fabra University, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3791-8814","authenticated-orcid":false,"given":"Ana","family":"Aldea-Perona","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Life Sciences, Pompeu Fabra University, 08003 Barcelona, Spain"},{"name":"Hospital del Mar Research Institute, 08003 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rosi-Schumacher, M., Baker, J., Waris, J., Seiffert-Sinha, K., and Sinha, A.A. (2023). Worldwide epidemiologic factors in pemphigus vulgaris and bullous pemphigoid. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1159351"},{"key":"ref_2","unstructured":"Borstnar, C.R., and Cardellach, F. (2020). Farreras Rozman. Medicina Interna, Elsevier. [19th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"a180","DOI":"10.1136\/bmj.a180","article-title":"Bullous pemphigoid and pemphigus vulgaris--incidence and mortality in the UK: Population based cohort study","volume":"337","author":"Langan","year":"2008","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1186\/s12967-021-03192-8","article-title":"Bullous pemphigoid in diabetic patients treated by gliptins: The other side of the coin","volume":"19","author":"Chouchane","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.ad.2012.10.022","article-title":"Penfigoide ampolloso: Gu\u00eda de manejo pr\u00e1ctico","volume":"105","year":"2014","journal-title":"Actas Dermosifiliogr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/dom.13129","article-title":"Incretin hormones: Their role in health and disease","volume":"20","author":"Nauck","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1016\/j.jid.2018.01.027","article-title":"Vildagliptin Significantly Increases the Risk of Bullous Pemphigoid: A Finnish Nationwide Registry Study","volume":"138","author":"Varpuluoma","year":"2018","journal-title":"J. Investig. Dermatol."},{"key":"ref_8","unstructured":"FDA (2025, October 05). Drug Safety Communication: FDA Adds Warnings About Heart Failure Risk to Labels of Type 2 Diabetes Medicines Containing Saxagliptin and Alogliptin; Content Current as of: 3 July 2018, Available online: https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-drug-safety-communication-fda-adds-warnings-about-heart-failure-risk-labels-type-2-diabetes."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Williams-Herman, D., Round, E., Swern, A.S., Musser, B., Davies, M.J., Stein, P.P., Kaufman, K.D., and Amatruda, J.M. (2008). Safety and tolerability of sitagliptin in patients with type 2 diabetes: A pooled analysis. BMC Endocr. Disord., 8.","DOI":"10.1186\/1472-6823-8-14"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2337\/dc12-0706","article-title":"Long-term efficacy and safety of linagliptin in patients with type 2 diabetes and severe renal impairment: A 1-year, randomized, double-blind, placebo-controlled study","volume":"36","author":"McGill","year":"2013","journal-title":"Diabetes Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"adv00224","DOI":"10.2340\/00015555-3457","article-title":"A Systematic Review of Drug-Induced Pemphigoid","volume":"100","author":"Verheyden","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"de Nicolas-Ruanes, B., Ballester-Martinez, A., Garcia-Mouronte, E., Berna-Rico, E., Azcarraga-Llobet, C., and Fernandez-Guarino, M. (2023). From Molecular Insights to Clinical Perspectives in Drug-Associated Bullous Pemphigoid. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242316786"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Hung, C.-T., Chang, Y.-L., and Wang, W.-M. (2022). Dipeptidyl Peptidase-4 Inhibitor-Related Bullous Pemphigoid: Clinical, Laboratory, and Histological Features, and Possible Pathogenesis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214101"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Lambadiari, V., Kountouri, A., Kousathana, F., Korakas, E., Kokkalis, G., Theotokoglou, S., Palaiodimou, L., Katsimbri, P., Ikonomidis, I., and Theodoropoulos, K. (2021). The association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors: A ten-year prospective observational study. BMC Endocr. Disord., 21.","DOI":"10.1186\/s12902-021-00689-7"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.jaad.2018.09.048","article-title":"Dipeptidyl-peptidase IV inhibitor-associated bullous pemphigoid: A systematic review and meta-analysis","volume":"85","author":"Kridin","year":"2021","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1111\/ajd.13100","article-title":"Dipeptidyl peptidase-4 inhibitors and bullous pemphigoid: A systematic review and adjusted meta-analysis","volume":"61","author":"Phan","year":"2020","journal-title":"Australas. J. Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1001\/jamadermatol.2020.1587","article-title":"Association Between Medication Use and Bullous Pemphigoid: A Systematic Review and Meta-analysis","volume":"156","author":"Liu","year":"2020","journal-title":"JAMA Dermatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.7150\/ijms.55421","article-title":"Bullous Pemphigoid and Diabetes medications: A disproportionality analysis based on the FDA Adverse Event Reporting System","volume":"18","author":"Huang","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1007\/s40257-021-00625-4","article-title":"DPP-4 Inhibitors and Increased Reporting Odds of Bullous Pemphigoid: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS) from 2006 to 2020","volume":"22","author":"Jedlowski","year":"2021","journal-title":"Am. J. Clin. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1080\/14740338.2019.1668373","article-title":"Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: A pharmacovigilance-pharmacodynamic\/pharmacokinetic assessment through an analysis of the vigibase\u00ae","volume":"18","author":"Carnovale","year":"2019","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1007\/s11096-020-01003-6","article-title":"Bullous pemphigoid associated with the use of dipeptidil peptidase-4 inhibitors: Analysis from studies based on pharmacovigilance databases","volume":"42","author":"Martin","year":"2020","journal-title":"Int. J. Clin. Pharm."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e130","DOI":"10.2337\/dc18-0210","article-title":"Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Disproportionality Analysis Based on the Japanese Adverse Drug Event Report Database","volume":"41","author":"Arai","year":"2018","journal-title":"Diabetes Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1177\/10600280211022722","article-title":"Analysis of the Clinical Characteristics of Dipeptidyl Peptidase-4 Inhibitor-Induced Bullous Pemphigoid","volume":"56","author":"Sun","year":"2022","journal-title":"Ann. Pharmacother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/bjd.14601","article-title":"Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: A case-noncase study in the French Pharmacovigilance Database","volume":"175","author":"Moulis","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.jaad.2017.12.038","article-title":"Dipeptidyl peptidase IV inhibitors, a risk factor for bullous pemphigoid: Retrospective multicenter case-control study from France and Switzerland","volume":"78","author":"Benzaquen","year":"2018","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1002\/pds.4847","article-title":"Cardiovascular risks associated with dipeptidyl peptidase-4 inhibitors monotherapy compared with other antidiabetes drugs in the Japanese population: A nationwide cohort study","volume":"28","author":"Komamine","year":"2019","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1111\/ijd.14658","article-title":"Bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitors. A case series and analysis of cases reported in the Spanish pharmacovigilance database","volume":"59","author":"Reolid","year":"2020","journal-title":"Int. J. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1111\/j.1365-2125.2011.04037.x","article-title":"Benefits and strengths of the disproportionality analysis for identification of adverse drug reactions in a pharmacovigilance database","volume":"72","author":"Montastruc","year":"2011","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"453","DOI":"10.2165\/00002018-200225060-00010","article-title":"Use of measures of disproportionality in pharmacovigilance: Three Dutch examples","volume":"25","author":"Egberts","year":"2002","journal-title":"Drug Saf."},{"key":"ref_30","unstructured":"European Medicines Agency (EMA) (2025, March 26). Pharmacovigilance: Research and Development: EudraVigilance. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/research-development\/pharmacovigilance-research-development\/eudravigilance."},{"key":"ref_31","unstructured":"European Medicines Agency (EMA) (2025, March 26). Januvia. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/januvia."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1800\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T10:19:23Z","timestamp":1764152363000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/12\/1800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,26]]},"references-count":31,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ph18121800"],"URL":"https:\/\/doi.org\/10.3390\/ph18121800","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,26]]}}}