Disentangling conflicting evidence on DPP-4 inhibitors and outcomes of COVID-19: narrative review and meta-analysis

Background: The infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread all over the world, becoming pandemic. Several studies have shown that diabetes mellitus (DM) is an independent risk factor that increases mortality and other adverse outcomes of coronavirus disease-19 (COVID-19). Studies have suggested that SARS-CoV-2 may bind dipeptidyl peptidase-4 (DPP4) for entering cells of the respiratory tract. Besides, DPP4 takes part in immune system regulation. Thus, DPP-4 inhibitors (DPP4i) may play a role against COVID-19. Methods: We focused on the impact of DPP4i treatment on COVID-19-related outcomes in people with DM. For this purpose, we conducted a systematic review and meta-analysis to summarize the existing evidence on this topic. Results: Retrospective observational studies provide inconsistent results on the association between use of DPP4i and outcomes of COVID-19. While two studies reported significantly lower mortality rates among patients with DM who received DPP4i versus those who did not, a series of other studies showed no effect of DPP4i or even worse outcomes. A meta-analysis of 7 studies yielded a neutral estimate of the risk ratio of COVID-19-related mortality among users of DPP4i (0.81; 95% CI 0.57–1.15). Conclusion: In the absence of randomized controlled trials, observational research available so far provides inconclusive results and insufficient evidence to recommend use of DPP4i against COVID-19.