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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Sep 15, 2021; 12(9): 1426-1441
Published online Sep 15, 2021. doi: 10.4239/wjd.v12.i9.1426
Dipeptidyl peptidase-4 inhibitor-induced autoimmune diseases: Current evidence
Ayan Roy, Jayaprakash Sahoo, Niya Narayanan, Chandhana Merugu, Sadishkumar Kamalanathan, Dukhabandhu Naik
Ayan Roy, Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, Jodhpur 342005, India
Ayan Roy, Jayaprakash Sahoo, Niya Narayanan, Chandhana Merugu, Sadishkumar Kamalanathan, Dukhabandhu Naik, Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
Author contributions: Sahoo J and Kamalanathan S conceptualized the work; Roy A wrote the first draft and provided critical inputs; Narayanan N and Merugu C prepared the first draft of the arthritis and the inflammatory bowel disease sections, respectively; Sahoo J, Naik D, and Kamalanathan S supervised the writing and critically revised the manuscript; Roy A, Sahoo J, and Kamalanathan S edited the final draft; all authors have read and approved the final version of the manuscript.
Conflict-of-interest statement: Dr. Sahoo has nothing to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non-Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jayaprakash Sahoo, MD, DM, Additional Professor, Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Room No. 5444, 4th Floor, Super Specialty Block, Puducherry 605006, India. jppgi@yahoo.com
Received: February 15, 2021
Peer-review started: February 15, 2021
First decision: March 30, 2021
Revised: April 12, 2021
Accepted: July 19, 2021
Article in press: July 19, 2021
Published online: September 15, 2021
Abstract

Dipeptidyl peptidase-4 inhibitors (DPP-4i) have an important place in the management of type 2 diabetes. The DPP-4 enzyme is ubiquitously distributed throughout the human body and has multiple substrates through which it regulates several important physiological functions. DPP-4 regulates several immune functions, including T-cell activation, macrophage function, and secretion of cytokines. Studies have reported an increase in autoimmune diseases like bullous pemphigoid, inflammatory bowel disease, and arthritis with DPP-4i use. The relationship of DPP-4i and autoimmune diseases is a complex one and warrants further research into the effect of DPP-4 inhibition on the immune system to understand the pathogenesis more clearly. Whether a particular cluster of autoimmune diseases is associated with DPP-4i use remains an important contentious issue. Nevertheless, a heightened awareness from the clinicians is required to identify and treat any such diseases. Through this review, we explore the clinical and pathophysiological characteristics of this association in light of recent evidence.

Keywords: Autoimmune disease, Bullous pemphigoid, Diabetes, Dipeptidyl peptidase-4 inhibitors, Gliptins, Inflammation

Core Tip: Dipeptidyl peptidase-4 (DPP-4) has an important role in the function of the immune system. DPP-4 inhibitors are an important drug class for the management of type 2 diabetes mellitus. This group of drugs can have a diverse effect on immune modulation. Recently, certain autoimmune diseases are described with the use of DPP-4 inhibitors, particularly bullous pemphigoid. Clinicians should be aware of this association and take appropriate action if such an adverse event takes place.