Understanding the Role of Dipeptidyl Peptidase-4 Inhibitors in COVID-19: Findings From a Systematic Review

Background: Inhibitors of dipeptidyl peptidase-4 (DPP4) have been used for diabetic patients and there is debate around using the same DPP4 inhibitors as a potential source of treatment for severe corona-virus disease 2019 (COVID-19). The findings from individual stud-ies regarding the usage of DDP4 inhibitors on COVID infection are available but not reviewed and synthesized. Therefore, we aimed to conduct a systematic review to synthesize the findings regarding its effect on the COVID infection course and the outcome. Methods: We carried out an electronic search in Google Scholar and PubMed. We considered a study eligible if it was an original research study, published in English during the era of COVID-19 till Septem-ber 2021, and had provided information on the topic of DPP4 inhibi-tors and COVID infection followed by reviewing the full-text articles and summarizing their findings. Results: This review provided novel insights into the effect of DDP4 inhibitor users and its effect on COVID-19 patients. Overall, litera-ture is scarce on the effect of DDP4 inhibitors on COVID severity and we found mixed results regarding the DDP4 effects on disease sever-ity and mortality. The evidence is not consistent currently as some of the studies supported the role of DDP4 inhibitor, while other stud-ies provided contradictory findings. UK population data published in 2021 with 2.5 million diabetic patients found no evidence to support a protective effect of DDP inhibitors on morbidity and mortality related to COVID-19. Conclusion: The findings of the review reveal that there is some ben-efit of the usage of DDP4 inhibitors on COVID-19 morbidity and mortality. However, we highly recommend replicating the studies in different contexts before making any strong recommendations. Furthermore, the results need to be interpreted cautiously due to the scarcity of literature on the role of DDP4 inhibitors among diabetic patients with COVID-19.