Outpatient metformin use is associated with reduced severity of COVID-19 disease in adults with overweight or obesity.

Background Observational studies suggest outpatient metformin use is associated with reduced mortality from COVID-19 disease. Metformin is known to decrease interleukin-6 (IL-6) and tumor-necrosis alpha (TNFα), which appear to contribute to morbidity in COVID-19. We sought to understand whether outpatient metformin use was associated with reduced odds of severe COVID-19 disease in a large US healthcare dataset. Methods Retrospective cohort analysis of electronic health record (EHR) data that was pooled across multiple EHR systems from 12 hospitals and 60 primary care clinics in the Midwest between March 4, 2020 - Dec 4, 2020. Inclusion criteria data for body mass index (BMI)>25kg/m2 and a positive SARS-CoV-2 PCR test; age ≥30 and ≤85 years. Exclusion criteria patient opt-out of research. Metformin is the exposure of interest, and death, admission, and ICU admission are the outcomes of interest. Results Metformin was associated with a decrease in mortality from COVID-19, OR 0.32 (0.15, 0.66, p=0.002), and in the propensity matched cohorts, OR 0.38 (0.16, 0.91, p=0.030). Metformin was associated with a non-significant decrease in hospital admission for COVID-19 in the overall cohort, OR 0.78 (0.58-1.04, p=0.087). Among the subgroup with a hemoglobin HbA1c available (n=1,193), the adjusted odds of hospitalization (including adjustment for HbA1c) for metformin users was OR 0.75 (0.53-1.06, p=0.105). Conclusions Outpatient metformin use was associated with a lower mortality and a trend towards decreased admission for COVID-19. Given metformin's low cost, established safety, and the mounting evidence of reduced severity of COVID-19 disease, metformin should be prospectively assessed for outpatient treatment of COVID-19. This article is protected by copyright. All rights reserved.