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

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Abstract

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.

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Author information

Authors and Affiliations

  1. Department of Dermatology, Rambam Health Care Campus, POB 9602, 31096, Haifa, Israel

    Khalaf Kridin

  2. Department of Dermatology, University of California, Irvine, CA, USA

    Kyle Amber

  3. Internal Medicine D and Institute of Endocrinology, Diabetes and Metabolism, Rambam Health Care Campus, Haifa, Israel

    Mogher Khamaisi

  4. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

    Mogher Khamaisi

  5. Department of Quality Measurements and Research, Chief Physician’s Office, Clalit Health Services, Tel Aviv, Israel

    Doron Comaneshter, Erez Batat & Arnon D. Cohen

  6. Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

    Arnon D. Cohen

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  1. Khalaf Kridin
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  2. Kyle Amber
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Correspondence to Khalaf Kridin.

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Kridin, K., Amber, K., Khamaisi, M. et al. Is there an association between dipeptidyl peptidase-4 inhibitors and autoimmune disease? A population-based study. Immunol Res 66, 425–430 (2018). https://doi.org/10.1007/s12026-018-9005-8

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