Preadmission Metformin Use Is Associated with Reduced Mortality in Patients with Diabetes Mellitus Hospitalized with COVID-19: Metformin in Diabetes Mellitus and COVID-19

Background Observational studies have reported an association between metformin and improved outcomes in COVID-19, but most have been small and with significant limitations. Objective To evaluate the association between preadmission metformin exposure and mortality in patients with diabetes mellitus hospitalized with coronavirus disease 2019 (COVID-19) infection. Design Retrospective cohort analysis using electronic health records extracted from the American Heart Association COVID-19 Registry. Participants Adults ( n = 11,993) with diabetes mellitus but without chronic kidney disease (CKD) or need for hemodialysis who were hospitalized with COVID-19 between January 25, 2020, and February 9, 2022. Main Measures We used propensity score modeling to address differences between metformin and non-metformin users prior to multivariable log-binomial models to examine the association between metformin use at time of hospital admission for COVID-19 infection and in-hospital death; composite of in-hospital death or discharge to hospice; composite of in-hospital death, discharge to hospice, or ICU admission; and composite of in-hospital death, discharge to hospice, ICU admission, or mechanical ventilation. Key Results Compared to metformin non-use, pre-admission metformin use was associated with lower risk of in-hospital death (risk ratio (RR) 0.81 [95% CI 0.75–0.90]); composite of in-hospital death or discharge to hospice (RR 0.79 [95% CI 0.74–0.87]); composite of in-hospital death, discharge to hospice, or ICU admission (RR 0.90 [95% CI 0.86–0.95]); and composite of in-hospital death, discharge to hospice, ICU admission, or mechanical ventilation (RR 0.9 [95% CI 0.84–0.98]). Metformin use was also associated with lower risk of death due to respiratory cause (RR 0.86 [95% CI 0.74–0.97]) but not cardiovascular (RR 0.84 [95% CI 0.58–1.2]) or other (RR 0.78 [95% CI 0.60–1.0]) causes. Conclusions Pre-admission metformin use was associated with lower risk of in-hospital mortality and markers of disease severity among adults with diabetes mellitus without CKD and not requiring hemodialysis who were hospitalized with COVID-19 infection.