New Insights into the Pleiotropic Actions of Dipeptidyl Peptidase-4 Inhibitors Beyond Glycaemic Control

Dipeptidyl peptidase-4 (DPP-4) is a multifunctional serine ectopeptidase that cleaves and modifies a plethora of substrates, including regulatory peptides, cytokines and chemokines. DPP-4 is implicated in the regulation of immune response, viral entry, cellular adhesion, metastasis and chemotaxis. Regarding its numerous substrates and extensive expression inside the body, multitasking DPP-4 has been assumed to participate in different pathophysiological mechanisms. DPP-4 inhibitors or gliptins are increasingly used for the treatment of type 2 diabetes mellitus. Several reports from experimental and clinical studies have clarified that DPP-4 inhibitors exert many beneficial pleiotropic effects beyond glycaemic control, which are mediated by anti-inflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic actions. The present review will highlight the most recent findings in the literature about these pleiotropic effects and the potential mechanisms underlying these benefits, with a specific focus on the potential effectiveness of DPP-4 inhibitors in coronavirus disease-19 and diabetic kidney disease.