key: cord-0935178-qhxjszp5
authors: Bouhanick, Béatrice; Cracowski, Jean-Luc; Faillie, Jean-Luc
title: DPP-4 inhibitors and severe course of illness in patients with COVID-19
date: 2021-01-18
journal: Therapie
DOI: 10.1016/j.therap.2021.01.051
sha: 5880901d0fe829624c823797c1cfdab6a31c4f87
doc_id: 935178
cord_uid: qhxjszp5

nan

patients dramatically increases as scientific data are rapidly published (more than 3500 publications on PUBMED in January 2021). Emerging evidence demonstrates that the degree of blood glucose control in patients infected with SARS-CoV-2 is of importance for the viral progression.

In 2020, we reported research data on antidiabetic drugs in this context and the potential influence of dipeptidyl peptidase-4 (DPP-4) inhibitors [1] . DPP-4 inhibitors target the enzymatic activity of DPP-4 and block the breakdown of GLP-1 and GIP leading to increased insulin secretion and reduced hyperglycemia in patients with type 2 diabetes. In addition to its effects on glucose metabolism, DPP-4 is also the T-cell antigen CD26 which is supposed to play a role in T-cell proliferation. Therefore, its inhibition was initially thought to potentially increase the risk of infection. However, other studies suggest that DPP-4 inhibition may have opposite effect. Being a ubiquitously transmembrane glycoprotein found on the surface of many cells with non-specific exopeptidase enzyme activity, human DPP-4 has been identified as a functional receptor for the spicule protein of the coronavirus which caused the Middle East Respiratory Syndrome (MERS).

The use of antibodies directed against DPP-4 resulted in inhibited MERS-CoV infection. Besides, DPP-4 was also found to increase inflammatory immune responses by modifying the production of several cytokines and chemokines. Another element of complexity is the fact that DPP-4 also exists as a soluble enzyme in the circulation. However, its role as a virus receptor or protector against it is currently totally unclear.

Whether diabetes treatment with DPP-4 inhibitors in clinical practice influences the course of the infection caused by COVID-19 is currently unknown. In the present issue of Therapies, Kow and Hasan showed the results of a meta-analysis to summarize the overall effect of DPP-4 inhibitors on the clinical outcomes in patients with COVID-19 [2] . Including six observational studies with overall 1,531 patients with COVID-19, neither beneficial nor harmful effect was evidenced when using DPP-4 inhibitors. These preliminary data seem therefore reassuring on that population and, at

Therapeutics (SFPT)

Diabetes and COVID-19

A meta-analysis on the preadmission use of DPP-4 inhibitors and risk of a fatal or severe course of illness in patients with COVID-19