DPP4 inhibitors and respiratory infection, a systematic review and meta-analysis of the CardioVascular Outcomes Trials conducted before the pandemic and implications for the management of diabetes during COVID-19

Grenet, G.; Mekhaldi, S.; MAINBOURG, S.; AUFFRET, M.; Cornu, C.; Cracowski, J.-L.; Gueyffier, F.; Lega, J.-C.; CUCHERAT, M.

Background Association between DPP4 inhibitors and respiratory infection remains unclear. CardioVascular Outcomes Trials (CVOTs) conducted before the COVID-19 pandemic are available. We aimed to estimate the effect of DPP4 inhibitors on the risk of respiratory infections. Methods We updated a previous systematic review and meta-analysis, searching for CVOTs assessing a DPP4 inhibitor in patients with type 2 diabetes mellitus. We focused on placebo-controlled CVOTs. Our primary outcome was 'any respiratory infection'. We added a sensitivity analysis integrating non-CVOTs and active-controlled CVOTs. Findings We included 47 714 patients in five placebo-controlled CVOTs. Median follow-up ranged from 1.5 years to 3 years. 4 369 events of overall respiratory infection were reported (rate of 9.2%). DPP4 inhibitors were not associated with a different risk compared to placebo (RR = 0.99 [95%CI: 0.93; 1.04]). The sensitivity analysis integrating the non-CVOTs studies and the active-controlled CVOT reached 11 349 events among 82 644 participants (rate of 13.7%). DPP4 inhibitors were not associated with a different risk of overall respiratory infection (RR = 1.00 [95% CI: 0.97; 1.03]). Interpretation Our up-dated meta-analysis provides the most powerful and least biased estimation of the association of DPP4 inhibitors and the risk of overall (non COVID-19) respiratory infection. We did not find any effect of the DPP4 inhibitors on the risk of respiratory infection. Our results support the recently published practical recommendations for the management of diabetes in patients with COVID-19, suggesting that DPP4 inhibitors should not be discontinued regarding the COVID-19 pandemic.