Metformin use before COVID-19 vaccination and the risks of COVID-19 incidence, medical utilization, and all-cause mortality in patients with type 2 diabetes mellitus

AIMS: We designed this study to determine whether metformin use before COVID-19 vaccination influences the risk of COVID-19 infection, medical utilization, and mortality. METHODS: We used the US collaborative network of TriNetX to identify 123,709 patients with type 2 diabetes mellitus fully vaccinated against COVID-19 between January 1, 2020, and November 22, 2022. The study selected 20,894 pairs of metformin users and nonusers by propensity score matching. The Kaplan-Meier method and Cox proportional hazards models were used to compare the risks of COVID-19 infection, medical utilization, and mortality between the study and control groups. RESULTS: No significant difference was noted between metformin users and nonusers in the risk of COVID-19 incidence (aHR = 1.02, 95% CI = 0.94–1.10). Compared to the control cohort, the metformin cohort exhibited a significantly lower risk of hospitalization (aHR = 0.85, 95% CI = 0.81–0.89), critical care services (aHR = 0.81, 95% CI = 0.70–0.94), mechanical ventilation (aHR = 0.75, 95% CI = 0.60–0.95), and mortality (aHR = 0.75, 95% CI = 0.63–0.89). The subgroup analyses and sensitivity analysis showed similar results. CONCLUSION: The present study showed that metformin use before COVID-19 vaccination could not reduce COVID-19 incidence; however, it was associated with significantly lower risks of hospitalization, intensive care service, mechanical ventilation, and mortality in fully vaccinated type 2 diabetes mellitus patients.