DPP-4 Inhibitors in the Prevention/Treatment of Pulmonary Fibrosis, Heart and Kidney Injury Caused by COVID-19—A Therapeutic Approach of Choice in Type 2 Diabetic Patients?

Abstract

Since the outbreak of SARS-CoV-2 virus more than 12,500,000 cases have been reported worldwide. Patients suffering from diabetes and other comorbidities are particularly susceptible to severe forms of the COVID-19, which might result in chronic complications following recovery. Dipeptidyl peptidase-4 inhibitors exert beneficial effects in prevention/treatment of pulmonary fibrosis, heart, and kidney injury, and since they may be a long-term consequence caused by COVID-19, it is reasonable to expect that DPP-4 inhibitors might be beneficial in alleviating long-term consequences of COVID-19. With that in mind, we would like to voice our concerns over chronic implications following recovery from COVID-19, especially not only in diabetic but also in non-diabetic patients, and to indicate that some preventive measures could be undertaken by application of DPP-4 inhibitors.

The Association Between Hypoglycemic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis

“…Although current evidence supports metformin use, further studies are needed to understand its mechanistic link to mortality benefits. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in The copyright holder for this this version posted January 27, 2021. ; https://doi.org/10.1101/2021.01.26.21250506 doi: medRxiv preprint proliferating vascular smooth muscle cells to avoid adverse outcomes (17). As DPP-4 is hypothesized to be a binding partner for corona-like viruses to enter host immune cells, DPP-4i also exerts influence on prohibiting invasion of SARS-CoV-2 into cells (49).…”

“…Previous studies comparing the prevalence of DPP-4i use between diabetic patients with or without COVID-19 showed that DPP-4i use was more prevalent in COVID-19 patients(47), implying that DPP-4i might not prevent people from contracting SARS-CoV-2(48). However, some opinions indicated that diabetic patients with COVID-19 could benefit from DPP-4i not only by controlling blood glucose, but also improving long-term prognosis of COVID-19 caused by pulmonary fibrosis, heart and kidney injury via blocking the tissue remodeling function of activating myofibroblasts and migrating fibroblasts, suppressing inflammatory sign and proliferating vascular smooth muscle cells to avoid adverse outcomes(17). As DPP-4 is hypothesized to be a binding partner for corona-like viruses to enter host immune cells, DPP-4i also exerts influence on prohibiting invasion of SARS-CoV-2 into cells(49).…”

“…Five clinical trials have been registered thus far, and previous reports of effects of metformin on clinical prognosis of COVID-19 remain controversial(15, 16). DPP-4i, another commonly used antidiabetic drug, might not protect people from infection as reported in a large case-control study in which DPP-4i was more prevalent in diabetic patients with confirmed COVID-19 than those without COVID-19, but might still play an important role in protecting COVID-19 patients from organ failure and evolving pneumonia to pulmonary fibrosis(17). A clinical trial is ongoing in France to assess the efficacy of several repurposed drugs against COVID-19 including repaglinide(18).…”

Physiological and Immunological Causes of the Susceptibility of Chronic Inflammatory Patients to COVID-19 Infection: Focus on Diabetes

“…Therefore, DPP4 inhibitors exert their anti-inflammatory functions on different cell types such as macrophages, T cells, and lung cells. In addition, it seems that DPP4 inhibitors have some anti-fibrotic effects on the lung by affecting the proliferative and inflammatory-signaling-pathways of human pulmonary arterial smooth muscle cells and fibroblasts ( 63 ).…”

Use of dipeptidyl peptidase‐4 inhibitors and prognosis of COVID‐19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO study

“…The literature already includes papers questioning a wide use of the class for preventing COVID-19 and its complications. 29 As thoroughly discussed in a commentary paper, 30 all these studies have strong limitations (some of which were shared by our current work, first of all their observational nature). These limitations were probably balanced by the potential importance of their messages during the editorial process, because of the emergency context of the ongoing pandemic.…”