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

touchREV Endocrinol. 2024 Oct;20(2):19-29. doi: 10.17925/EE.2024.20.2.5. Epub 2024 Sep 6.

Abstract

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.

Keywords: Antioxidants; coronavirus; diabetes mellitus; diabetic nephropathies; dipeptidyl peptidase-4; dipeptidyl peptidase-4 inhibitors; glucagon-like peptide-1; pleiotropic actions.

Publication types

  • Review

Grants and funding

Support: No funding was received in the publication of this article.