Abstract: PLOS ONE RESEARCH ARTICLE Is metformin use associated with low mortality in patients with type 2 diabetes mellitus hospitalized for COVID-19? a multivariable and propensity score-adjusted meta-analysis Zhiyuan Ma ID, Mahesh Krishnamurthy ID* a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 Department of Medicine, St Luke’s University Health Network-Easton Campus, Easton, Pennsylvania, United States of America * Mahesh.Krishnamurthy@sluhn.org Abstract OPEN ACCESS Citation: Ma Z, Krishnamurthy M (2023) Is metformin use associated with low mortality in patients with type 2 diabetes mellitus hospitalized for COVID-19? a multivariable and propensity score-adjusted meta-analysis. PLoS ONE 18(2): e0282210. https://doi.org/10.1371/journal. pone.0282210 Editor: Jennifer A. Hirst, University of Oxford, UNITED KINGDOM Background Coronavirus disease 2019 (COVID-19) is a new pandemic that the entire world is facing since December of 2019. Increasing evidence has shown that metformin is linked to favorable outcomes in patients with COVID-19. The aim of this study was to address whether outpatient or inpatient metformin therapy for type 2 diabetes mellitus is associated with low inhospital mortality in patients hospitalized for COVID-19. Received: November 29, 2021 Accepted: February 6, 2023 Published: February 23, 2023 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0282210 Copyright: © 2023 Ma, Krishnamurthy. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Methods We searched studies published in PubMed, Embase, Google Scholar and Cochrane Library up to November 1, 2022. Raw event data extracted from individual study were pooled using the Mantel-Haenszel approach. Odds ratio (OR) or hazard ratio (HR) adjusted for covariates that potentially confound the association using multivariable regression or propensity score matching was pooled by the inverse-variance method. Random effect models were applied for meta-analysis due to variance among studies. Results Twenty-two retrospective observational studies were selected. The pooled unadjusted OR for outpatient metformin therapy and in-hospital mortality was 0.48 (95% CI, 0.37–0.62) and the pooled OR adjusted with multivariable regression or propensity score matching was 0.71 (95% CI, 0.50–0.99). The pooled unadjusted OR for inpatient metformin therapy and in-hospital mortality was 0.18 (95% CI, 0.10–0.31), whereas the pooled adjusted HR was 1.10 (95% CI, 0.38–3.15). PLOS ONE | https://doi.org/10.1371/journal.pone.0282210 February 23, 2023 1 / 13 PLOS ONE Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Metformin in patients with Type 2 diabetes mellitus hospitalized for COVID-19 Conclusions Our results suggest that there is a significant association between the reduction of in-hospital mortality and outpatient metformin..