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Meta-Analysis
. 2021 Jul;44(7):1379-1386.
doi: 10.1007/s40618-021-01515-6. Epub 2021 Jan 29.

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

B M Bonora  1 , A Avogaro  1 , G P Fadini  2
Affiliations
Meta-Analysis

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

B M Bonora et al. J Endocrinol Invest. 2021 Jul.

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 (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.

Keywords: Coronavirus; Diabetes; Epidemiology; Incretins; Pandemic.

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Conflict of interest statement

B.M.B. received lecture or advisory board fees from Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Mundipharma, Novartis, Novo Nordisk, and Sanofi. A.A. received research grants, lecture fees, or advisory board fees from Merck Sharp & Dome, AstraZeneca, Novartis, Boehringer Ingelheim, Sanofi, Mediolanum, Janssen, Novo Nordisk, Eli Lilly, Servier, and Takeda. G.P.F. received grant support, lecture fees, or advisory board fees from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, Sanofi, Genzyme, Servier, and Merck Sharp & Dohme.

Figures

Fig. 1
Fig. 1
Risk for mortality for DPP4i users and other glucose-lowering medication users (crude data). Risk ratio with 95% confidence intervals
Fig. 2
Fig. 2
Risk for mortality for DPP4i users and other glucose-lowering medication users (adjusted risk ratio). Risk ratio with 95% confidence intervals
Fig. 3
Fig. 3
Interpretation of a possible spurious association between use of DPP4i and better outcomes of COVID-19. Specific clinical characteristics are typically associated with the probability of receiving a DPP4i. In addition, having attended diabetes clinics before COVID-19 or being seen by a diabetes specialist during hospitalization increases the likelihood of receiving a DPP4i. In both cases, the observed outcome can be confounded by different clinical characteristics or by indirect effect of diabetes specialist care. Thus, the direct link between use of DPP4i and lower mortality is highlighted with a question mark
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