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

Abstract

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 . 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.

Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis

“…Use of DPP-4i for diabetic patients is associated with statistically non-significant reduced mortality risk or poor composite outcomes of COVID-19 according to our analysis. This was consistent with previous meta-analyses ( 57 ) but was conflicting with the other research ( 58 , 59 ). Previous studies comparing the prevalence of DPP-4i use between diabetic patients with or without COVID-19 showed that DPP-4i use was more prevalent in COVID-19 patients ( 60 ), implying that DPP-4i might not prevent people from contracting SARS-CoV-2 ( 61 ).…”

Managing diabetes in diabetic patients with COVID: where do we start from?

“…Our research found no significant difference in the rate of intensive care unit (ICU) admission or death between DPP-4i users and non-users [ 33 , 42 ]. Furthermore, we observed that the rate of DPP-4i use was also similar in patients with diabetes mellitus hospitalized with COVID-19 pneumonia and with pneumonia of other etiology.…”

“…Other studies with a smaller number of patients confirmed these results. In a meta-analysis of 7 studies, we found an unbiased estimate of the risk ratio of COVID-19-related mortality among users of DPP4i (0.81; 95% CI 0.57–1.15) [ 42 ]. At variance, in their study, Khunti and colleagues have found that treatment with DPP-4i was associated with a small 1.07 (1.01–1.13) but significant increase in mortality [ 19 ].…”

Dipeptidyl Peptidase-4 Inhibitors and COVID-19-Related Deaths among Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Observational Studies

“…A previously published metaanalysis of six observational studies by Kow and Hasan [5] addressing the composite outcome of severe or fatal illness demonstrated that pre-admission use of DPP-4 inhibitors did not have a significant impact on prespecified outcomes. More recently, Bonora et al [6] pooled data from seven observational studies published in the Journal of Endocrinological Investiga-…”