key: cord-0707089-wviuhx4w
authors: Kow, Chia Siang; Hasan, Syed Shahzad
title: Use of DPP-4 inhibitors in patients with COVID-19
date: 2020-11-17
journal: Acta Diabetol
DOI: 10.1007/s00592-020-01629-y
sha: 2c73abf4eb18f66941430c3bc61db7e5f4ee8441
doc_id: 707089
cord_uid: wviuhx4w

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DPP-4 also acts on the vascular system where it possesses anti-thrombotic properties and may act as an immobilized anticoagulant on endothelial cells. This is owing to their ability to inhibit fibrin polymerization and clot formation.

In vivo model has demonstrated a reduction in the expression and activity of DPP-4 within the infarction area of patients with acute myocardial infarction, which corresponded to an increase in pro-coagulant Tissue Factor expression, suggesting a shift toward a prothrombogenic status [4] . Furthermore, when human umbilical vein endothelial cells were treated with diprotin A which inhibits the activity of DPP-4, increased adherence of non-stimulated platelets under flow conditions was observed, corresponding to a sign of thrombogenicity [4] .

Real-world data have also indicated a safety signal with DPP-4 inhibitors due to the increased reporting of venous thromboembolism events. A recent pharmacovigilance study [5] observed excess of reporting of venous thromboembolism events with DPP-4 inhibitors compared with other antidiabetic agents except for insulin, with a proportional reporting ratio of 2·0 (95% confidence interval 1.7-2.3). In the post hoc subgroup analysis considering separately sitagliptin and other DPP-4 inhibitors, sitagliptin was associated with a significantly higher probability of reporting of venous thromboembolism events, with a proportional reporting ratio of 3.2 (95% confidence interval 2.8-3.7).

Although no definite conclusion could be made to the effect of DPP-4 inhibitors in COVID-19 patients, it may be unwise to repurpose DPP-4 inhibitors for the treatment of COVID-19 which is associated with a hypercoagulability state. In addition, in the aforementioned pharmacovigilance study [5] , almost 50% of venous thromboembolism events associated with DPP-4 inhibitors were co-reported with an infection, which demanded cautious use of DPP-4 inhibitors, especially sitagliptin, during an active infection such as COVID-19.

Dipeptidyl peptidase-4 (DPP4) inhibition in COVID-19

Venous thromboembolism in critically ill COVID-19 patients receiving prophylactic or therapeutic anticoagulation: a systematic review and meta-analysis

COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia

Loss of DPP4 activity is related to a prothrombogenic status of endothelial cells: implications for the coronary microvasculature of myocardial infarction patients

DPP-4 inhibitors and venous thromboembolism: an analysis of the WHO spontaneous reporting database