Biguanides Associate with Decreased Early Mortality and Risk of Acute Kidney Injury In Hospitalized COVID-19 Patients: a nationwide retrospective cohort study in Japan

BackgroundBiguanide (BG) is the most-prescribed oral glucose-lowering medication worldwide and has potential for further therapeutic applications. The Coronavirus disease 2019 (COVID-19) pandemic is a global public health emergency. Nevertheless, there are still no established low-cost treatments against COVID-19, of which the morbidity and mortality rates varing from country to country. Therefore, a nationwide study of the COVID-19 affected population is essential to explore therapeutic effect of BG against COVID-19. MethodsFrom the inpatient databases in Japan, covering the period from September 2021 to March 2023, which encompasses the era following the development of COVID-19 vaccines, we extracted data of 168,370 COVID-19 patients aged 20 to under 80 years who were suffered from diabetes mellitus treated with oral antidiabetic agents. The primary outcome was 100-day in-hospital mortality, and secondary outcome was the incidence of acute kidney injury (AKI) during hospitalization. We compared outcomes in patients who received BG with those in patients who did not, using a logistic regression analysis and Cox proportional hazards under both propensity score-unmatched and matched cohorts. ResultsThe incidence of in-hospital death was significantly lower in the BG group (1.18 %) compared to the non-BG group (2.41%) (p < 0.001). Similarly, the incidence of AKI during hospitalization was significantly lower in the BG group (0.66 %) compared to the non-BG group (1.12%) (p < 0.001). Kaplan-Meier analysis from the propensity-score matched cohort showed a significantly better survival rate in the BG group (adjusted HR, 0.580; 95% CI 0.510-0.658; p < 0.001). ConclusionIn COVID-19 patients, the use of oral biguanide use may be associated with a reduced in-hospital mortality and risk of AKI.