Safety of Dipeptidyl Peptidase-4 Inhibitors in COVID-19: AnUpdate

Abstract

Background: Safety of use of dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes and coronavirus disease 2019 (COVID-19) is unclear. Objective: To review the most recent data regarding safety of use of DPP-4 inhibitors before and during hospitalization of patients with type 2 diabetes and COVID-19.

Methods: PUBMED search until February 16, 2021. Search terms included COVID-19, DPP-4 inhibitors, sitagliptin, CD26, mortality, diabetes. Retrospective studies, pertinent animal investigations and pre-print studies are reviewed. 

Results: All available studies related to the use of DPP-4 inhibitors in patients with COVID-19 are retrospective. Very limited and conflicting data exist regarding susceptibility of patients using DPP-4 inhibitors to COVID-19. In one Italian study, use of the DPP-4 inhibitor, sitagliptin prior to hospital admission, was associated with reduction in mortality in patients with type 2 diabetes and COVID-19. In addition, the use of sitagliptin before hospitalization was associated with greater number of hospital discharges, 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 3 studies, pre-admission use of DPP-4 inhibitors was continued in most patients after admission. Two of these 3 studies did not show significant mortality benefit with the use of DPP-4 inhibitors, whereas the third and smallest study demonstrated significant reduction in in-hospital mortality. Results of 2 meta-analyses showed a neutral effect of DPP-4 inhibitors on mortality in patients with type 2 diabetes and COVID-19 admitted to the hospital.

Conclusions: Overall, use of DPP-4 inhibitors in patients with type 2 diabetes and COVID-19 may be safe whether these agents were stopped or continued after hospital admission. A possible beneficial effect of DPP-4 inhibitors on mortality cannot be excluded. Randomized trials are urgently needed to clarify the efficacy and safety of DPP-4 inhibitors in patients with COVID-19 with and without type 2 diabetes.