Abstract: Journal of Thrombosis and Thrombolysis https://doi.org/10.1007/s11239-022-02631-7 Metformin use in patients hospitalized with COVID‑19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes Abira Usman1 · Kevin P. Bliden1 · Alastair Cho1 · Naval Walia1 · Christophe Jerjian1 · Arvind Singh1 · Parshotam Kundan1 · Sanchit Duhan1 · Udaya S. Tantry1 · Paul A. Gurbel1 Accepted: 30 December 2021 © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022 Abstract Diabetes mellitus (DM) is associated with a greater risk of COVID-19 and an increased mortality when the disease is contracted. Metformin use in patients with DM is associated with less COVID-19-related mortality, but the underlying mechanism behind this association remains unclear. Our aim was to explore the effects of metformin on markers of inflammation, oxidative stress, and hypercoagulability, and on clinical outcomes. Patients with DM on metformin (n = 34) and metformin naïve (n = 41), and patients without DM (n = 73) were enrolled within 48 h of hospital admission for COVID-19. Patients on metformin compared to naïve patients had a lower white blood cell count (p = 0.02), d-dimer (p = 0.04), urinary 11-dehydro thromboxane ­B2 (p = 0.01) and urinary liver-type fatty acid binding protein (p = 0.03) levels and had lower sequential organ failure assessment score (p = 0.002), and intubation rate (p = 0.03), fewer hospitalized days (p = 0.13), lower in-hospital mortality (p = 0.12) and lower mortality plus nonfatal thrombotic event occurrences (p = 0.10). Patients on metformin had similar clinical outcomes compared to patients without DM. In a multiple regression analysis, metformin use was associated with less days in hospital and lower intubation rate. In conclusion, metformin treatment in COVID-19 patients with DM was associated with lower markers of inflammation, renal ischemia, and thrombosis, and fewer hospitalized days and intubation requirement. Further focused studies are required to support these findings. Keywords COVID-19 · Diabetes · Metformin · Thromboelastography · Biomarker · Death · Intubation Highlights • Fasting blood glucose level in patients with COVID-19 has been shown to be associated with severity of the disease and poor outcomes, including mortality. • Metformin use in patients with DM is associated with less COVID-19-related mortality, but the underlying mechanism behind this association remains unclear. • In this single center study, metformin treatment in COVID-19 patients with DM was associated with lower * Paul A. Gurbel pgurbel@lifebridgehealth.org 1 Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Lifebridge Health, Baltimore, MD 21215, USA markers of inflammation, renal ischemia, and thrombosis, and fewer hospitalized days and intubation requirement. • In a multiple regression analysis, metformin use was associated with less days in hospital and lower intubation rate.