key: cord-0757876-3pcinrzj
authors: Kokic Males, Visnja
title: Letter to the Editor in response to the article “COVID-19 and diabetes: Can DPP4 inhibition play a role?”
date: 2020-04-23
journal: Diabetes Res Clin Pract
DOI: 10.1016/j.diabres.2020.108163
sha: 444cd13a02e112d94829ff6d87c508be2c1811de
doc_id: 757876
cord_uid: 3pcinrzj

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In recently published commentary, Iacobellis [1] reported potential role of dipeptidyl peptidase 4 (DPP4) in coronavirus disease 2019 (COVID -19) infected people with type 2 diabetes. Results reported by Ray at al. [2] on another coronavirus (human coronavirus Erasmus Medical Center (hCoV-EMC) showed that antibodies directed against DPP4 inhibited hCoV-EMC infection of primary human bronchial epithelial cells . Also, Ray at al. reported that hCoV-EMC infection could not be blocked by DPP4 inhibitors such as vildaglipitn, sitagliptin, and saxagliptin. Another placebo-controlled randomised clinical trial showed decrease in lymphocyte count among saxagliptin users [3] .

Other than inactivating incretin hormones, DPP4 inhibitors have also other effects including those on immune system which may lead to increased infection risk [4] . A reduction of T-cell activity with DPP4 inihibition has been seen in vitro studies [5, 6] . Even though meta-analysis by Yang at al. [7] showed that upper respiratory tract infections does not increase significantly with DPP4 inhibitor treatment, another study by Willemen et al. reported opposite [4] . In this study infections were two times more frequently reported for DPP4 inhibitors compared with biguanides [4] . Overall, the immune response is impaired in patients with diabetes, and there is increasing evidence that DPP4 inhibitors may result in suppression of the immune system and may increase the risk of infections such as pneumonia [4, [8] [9] [10] . Upper respiratory tract infections can eventually lead to a serious or life-threatening condition, such as epiglottitis or pneumonia [11] , especially in persons with type 2 diabetes.

Even though the patients with type 2 diabetes are exposed to low grade chronic inflammation [1] which can cause an abnormal immune response, it is still unclear whether DPP4 has a potential role in COVID-19. So we mustn't run to presume that DPP4 inhibitors can reduce the risk of acute respiratory complications in type 2 diabetes with COVID-19 infection, and for now we need to distinguish DPP4 inhibition from DPP4 inhibitors until future studies show different.

COVID-19 and diabetes: Can DPP4 inhibition play a role?

Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC

CV181-011 Study Investigators. Effect of saxagliptin monotherapy in treatment -naive patients with type 2 diabetes

Use of dipeptidyl peptidase-4 inhibitors and the reporting of infections: a disproportionaly analysis in the World Health Organization VigiBase, Diabetes Care

Dual inhibition of dipeptidyl peptidase IV and aminopeptidase N suppresses inflammatory immune responses

Dipeptidyl ppeptidase IV inhibition for the treatment of typer 2 diabetes:potential importance of selectivity over dipeptiryl peptidases 8 and 9

DPP-4 inhibitors and risk of infections: a meta-analysis of randomized controlled trials

Dual inhibition of dipeptidyl petidase IV and aminopeptidase N suppresses inflammatory immune responses

Dipeptidyl peptidase IV inhibition for the treatment of type 2 diabetes: potential importance of selectivity over dipeptidyl peptidases 8 and 9

Upper Respiratory Tract Infection

Upper Respiratory Tract Infection

Declaration of Competing Interest The author, Višnja Kokić Maleš declares no conflict of interest