Dipeptidyl peptidase-4 inhibitor-induced autoimmune diseases: Current evidence

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.