Abstract: ORIGINAL RESEARCH published: 13 January 2021 doi: 10.3389/fendo.2020.600439 Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes Andrew B. Crouse 1, Tiffany Grimes 2, Peng Li 3, Matthew Might 1, Fernando Ovalle 2 and Anath Shalev 2* 1 Hugh Kaul Precision Medicine Institute, University of Alabama at Birmingham, Birmingham, AL, United States, Comprehensive Diabetes Center, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL, United States, 3 School of Nursing, University of Alabama at Birmingham, Birmingham, AL, United States 2 Edited by: Hans Ulrich Häring, Tübingen University Hospital, Germany Reviewed by: Abdurezak Ahmed Abdela, Addis Ababa University, Ethiopia Mohd Ashraf Ganie, Sher-I-Kashmir Institute of Medical Sciences, India *Correspondence: Anath Shalev shalev@uab.edu Specialty section: This article was submitted to Clinical Diabetes, a section of the journal Frontiers in Endocrinology Received: 30 August 2020 Accepted: 07 December 2020 Published: 13 January 2021 Citation: Crouse AB, Grimes T, Li P, Might M, Ovalle F and Shalev A (2021) Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes. Front. Endocrinol. 11:600439. doi: 10.3389/fendo.2020.600439 Background: Coronavirus disease-2019 (COVID-19) is a growing pandemic with an increasing death toll that has been linked to various comorbidities as well as racial disparity. However, the specific characteristics of these at-risk populations are still not known and approaches to lower mortality are lacking. Methods: We conducted a retrospective electronic health record data analysis of 25,326 subjects tested for COVID-19 between 2/25/20 and 6/22/20 at the University of Alabama at Birmingham Hospital, a tertiary health care center in the racially diverse Southern U.S. The primary outcome was mortality in COVID-19-positive subjects and the association with subject characteristics and comorbidities was analyzed using simple and multiple linear logistic regression. Results: The odds ratio of contracting COVID-19 was disproportionately high in Blacks/ African-Americans (OR 2.6; 95% CI 2.19–3.10; p<0.0001) and in subjects with obesity (OR 1.93; 95% CI 1.64–2.28; p<0.0001), hypertension (OR 2.46; 95% CI 2.07–2.93; p<0.0001), and diabetes (OR 2.11; 95% CI 1.78–2.48; p<0.0001). Diabetes was also associated with a dramatic increase in mortality (OR 3.62; 95% CI 2.11–6.2; p<0.0001) and emerged as an independent risk factor in this diverse population even after correcting for age, race, sex, obesity, and hypertension. Interestingly, we found that metformin treatment prior to diagnosis of COVID-19 was independently associated with a significant reduction in mortality in subjects with diabetes and COVID-19 (OR 0.33; 95% CI 0.13– 0.84; p=0.0210). Conclusion: Thus, these results suggest that while diabetes is an independent risk factor for COVID-19-related mortality, this risk is dramatically reduced in subjects taking metformin prior to diagnosis of COVID-19, raising the possibility that metformin may provide a protective approach in this high risk population. Keywords: African-American, coronavirus disease-2019, diabetes, metformin, mortality Frontiers in Endocrinology | www.frontiersin.org 1 January 2021 | Volume 11 | Article 600439 Crouse et al. Metformin Reduced COVID-19 Mortality analysis. This may have been due to..