# Biguanides are associated with decreased early mortality and risk of acute kidney injury in hospitalised patients with COVID-19: a nationwide retrospective cohort study in Japan

## TL;DR

Biguanides, a type of diabetes medication, may reduce early death and kidney injury risk in hospitalized COVID-19 patients with diabetes.

## Contribution

This study shows biguanides are linked to lower mortality and acute kidney injury in hospitalized diabetic COVID-19 patients.

## Key findings

- Patients on biguanides had 1.18% in-hospital death vs. 2.41% in non-biguanide users.
- Biguanide users had 0.66% acute kidney injury vs. 1.12% in non-users.
- Survival rates were better in biguanide users (adjusted HR 0.619).

## Abstract

The most prescribed oral glucose-lowering medication worldwide is biguanide (BG), which shows potential for further therapeutic applications. The coronavirus disease 2019 (COVID-19) pandemic is a global public health emergency. Nevertheless, low-cost treatments against COVID-19 have not been established, with varying morbidity and mortality rates in each country.

From the inpatient databases in Japan from September 2021 to March 2023, which includes the era following the development of COVID-19 vaccines, we extracted data from 168,370 patients with COVID-19 aged 20– < 80 years with diabetes mellitus treated with oral antidiabetic agents. The primary and secondary outcomes were 100-day in-hospital mortality and incidence of acute kidney injury (AKI) during hospitalisation, respectively. We compared outcomes in patients who received BG with those who did not using a logistic regression analysis and Cox proportional hazards under both propensity score-unmatched and matched cohorts.

The incidence of in-hospital death was significantly lower in the BG group (1.18%) compared with the non-BG group (2.41%) (P < 0.001). Similarly, the incidence of AKI during hospitalisation 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, 0.619; 95% CI, 0.545–0.702; P < 0.001).

In patients with COVID-19, oral biguanide use may be associated with reduced in-hospital mortality and AKI risk.

The online version contains supplementary material available at 10.1007/s10157-025-02755-z.