Oral Biguanide Use Is Associated with Lower Incidence of AKI and Mortality in COVID-19 Patients: A Nationwide Study Using the Diagnosis Procedure Combination System in Japan

Background: Recent studies have reported renoprotective effects of biguanides (BG), but their effectiveness in COVID-19 patients remains unclear. Methods: From the 2021 and 2022 DPC inpatient databases, which cover the era following the development of COVID-19 vaccines, we extracted data on 106,161 COVID-19 patients aged 20 to under 70 years who also had diabetes treated with oral antidiabetic agents including biguanides, dipeptidyl peptidase-4 inhibitors (DPP-4), sodium-glucose cotransporter type 2 inhibitors (SGLT2), sulfonylureas (SU), alpha-glucosidase inhibitors (aGI), glucagon-like peptide-1 (GLP-1) analogs, thiazolidinediones (TZD). Using propensity score matching, based on variables such as age, sex, BMI, and chronic kidney disease stage, we compared two groups: those taking BG medications (n = 7997) and those not taking BG medications (non-BG group, n = 7997). The primary outcome was in-hospital mortality, and the secondary outcome was the incidence of acute kidney injury (AKI) during hospitalization. Logistic regression analysis and Cox proportional hazards models were used for analysis. Results: The incidence of in-hospital mortality was significantly lower in the BG group (0.7%) compared to the non-BG group (1.2%) (p = 0.002). Similarly, the incidence of AKI during hospitalization was significantly lower in the BG group (0.7%) compared to the non-BG group (1.1%) (p = 0.025). Kaplan-Meier analysis showed a significantly better survival rate in the BG group (hazard ratio 0.675, 95% confidence interval 0.484-0.941, p < 0.0001). Conclusion: In COVID-19 patients, oral biguanide use may be associated with a reduced risk of AKI and in-hospital mortality.Kaplan–Meier estimates of all-cause mortality for COVID 19 patients with DM stratified by biguanide medication usage