Do DPP-4 Inhibitors Protect against COVID-19?

Abstract

Background: Limited retrospective data suggest that the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin may decrease mortality in patients with type 2 diabetes admitted with coronavirus disease 2019 (COVID-19). Objective: To review the strength of evidence that supports possible protective role of sitagliptin in COVID-19. Methods: PUBMED search until October 5, 2020. Search terms included COVID-19, sitagliptin, DPP-4, CD26, mortality, diabetes. Retrospective studies and pertinent animal and human studies are reviewed. Results: One retrospective study (n=338) showed that sitagliptin use before hospitalization was associated with significant mortality reduction of approximately 60% in patients with type 2 diabetes and COVID-19. Pre-admission sitagliptin administration was associated with greater number of hospital discharge, improvement of clinical status, reduced risk of transfer to intensive care unit (ICU) and need for mechanical ventilation compared with patients who were not receiving sitagliptin. In addition, there was significant decrease in some pro-inflammatory markers in the sitagliptin group. Another small retrospective study of 9 patients who were taking a DPP-4 inhibitor prior to admission did not find any significant effect of DPP-4 inhibitors on mortality and clinical outcomes after hospitalization. Conclusions: Weak evidence from observational studies suggests possible beneficial effects of sitagliptin use before hospital admission in patients with type 2 diabetes and COVID-19. Randomized trials are urgently needed to clarify the efficacy and safety of in-hospital sitagliptin administration in patients with COVID-19 with and without type 2 diabetes.