Immunologic Research

, Volume 66, Issue 3, pp 425–430 | Cite as

Is there an association between dipeptidyl peptidase-4 inhibitors and autoimmune disease? A population-based study

  • Khalaf Kridin
  • Kyle Amber
  • Mogher Khamaisi
  • Doron Comaneshter
  • Erez Batat
  • Arnon D. Cohen
Original Article


The association of dipeptidyl peptidase-4 inhibitors (DPP4is) with autoimmune diseases is controversial. While these agents were proposed as a novel therapeutic approach for several inflammatory diseases by blocking T cell proliferation and cytokine production, they were found to trigger inflammatroy bowel disease, inflammatory arthritis and bullous pemphigoid. Our objective is to examine the association between DPP4i and autoimmune diseases. This study was conducted as a cross-sectional study utilizing the database of Clalit Health Services. The prevalence of 15 autoimmune-/immune-mediated diseases was compared between patients on DPP4i treatment and age-, sex-, and ethnicity-matched controls. Univariate analysis was performed using chi-square and the Student t test and multivariate analysis was performed using a logistic regression model. The study included 283 patients treated with DPP4i agents and 5660 age-, sex-, and ethnicity-matched diabetic control subjects. The prevalence of Crohn’s disease (1.1 vs. 0.3%; odds ratios (OR), 3.56; 95% CI, 1.04–12.21, P = 0.031), psoriasis (2.5 vs. 1.2%; OR, 2.12; 95% CI, 0.99–4.66; P = 0.050), and Hashimoto’s thyroiditis (16.6 vs. 12.6%; OR, 1.38; 95% CI, 1.00–1.91; P = 0.049) was significantly higher in patients on DPP4i treatment than in controls. The prevalence of the remaining autoimmune diseases did not differ significantly between DPP4i-treated patients and their matched control subjects. In conclusion, this population-based study demonstrates an association of DPP4i intake with three autoimmune and inflammatory diseases noted to be part of a distinct autoimmune cluster that includes multiple sclerosis, psoriasis, thyroiditis, bullous pemphigoid, and inflammatory bowel disease. Experimental studies are required to define the role of DPP4i in this autoimmune cluster.


Autoimmune diseases Dipeptidyl peptidase-4 inhibitors Psoriasis Crohn’s disease Hashimoto’s thyroiditis 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of DermatologyRambam Health Care CampusHaifaIsrael
  2. 2.Department of DermatologyUniversity of CaliforniaIrvineUSA
  3. 3.Internal Medicine D and Institute of Endocrinology, Diabetes and MetabolismRambam Health Care CampusHaifaIsrael
  4. 4.Rappaport Faculty of MedicineTechnion-Israel Institute of TechnologyHaifaIsrael
  5. 5.Department of Quality Measurements and Research, Chief Physician’s OfficeClalit Health ServicesTel AvivIsrael
  6. 6.Siaal Research Center for Family Medicine and Primary Care, Faculty of Health SciencesBen-Gurion University of the NegevBeer-ShevaIsrael

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