Preadmission use of DPP4i reduced risks of hyperinflammatory syndrome, in-hospital death or invasive mechanical ventilation in COVID-19 patients with type 2 diabetes: a territory-wide retrospective cohort study

Abstract

Objective: T2DM patients with COVID-19 were associated with increased risk of hyperinflammation and hence poor prognosis. Inconclusive evidence suggested that dipeptidyl peptidase-4 inhibitors (DPP4i) may have anti-inflammatory effect and preventing SARS-CoV-2 viral entry. This territory-wide retrospective cohort study evaluated the clinical outcomes associated with the pre-admission use of DPP4i for T2DM patients with COVID-19. Methods: Patients with T2DM admitted with COVID-19 between 21st January 2020 and 31st January 2021 in Hong Kong were observed from date of admission until the date of in-hospital death, hospital discharge or data cut-off date (30th April 2021). Exposure was defined as receiving DPP4i treatment from 90 days prior admission to the day before admission for COVID-19. The primary outcome was the incidence rate of hyperinflammatory syndrome. Multivariable logistic regression models weighted by inverse probability of treatment weighting using the propensity score were performed to estimate odds ratios (OR) and their 95% confidence intervals (CI) of event outcomes for exposure versus non-exposure. Results: Out of 1214 eligible patients at a median follow-up of 16 days with 30,035 person-days, 107 patients received DPP4i prior to COVID-19 hospitalization. Preadmission use of DPP4i was associated with a lower risk of hyperinflammatory syndrome (OR = 0.56, 95%CI 0.45 to 0.69, P < 0.001), composite outcome of in-hospital death or the need of invasive mechanical ventilation (OR = 0.71, 95%CI 0.54 to 0.93, P = 0.013) and reduced length of hospital stay among survivors (−4.82 days, 95%CI –6.80 to –2.84, P < 0.001). Moreover, DPP4i users incurred significantly lower cumulative healthcare costs from day-7 (US$7,877 vs US$10,246, P < 0.001) to day-90 (US$26,310 vs US$39,482, P < 0.001) than control. Conclusion: Our study may have shed light regarding hyperinflammatory dynamics in mild-to-moderate COVID-19 patients with T2DM, which may be informative to these patient cohorts and associated clinicians. However, prospective studies are necessary to further elucidate the potential role of DPP4i in the pathophysiology of T2DM and COVID-19.