Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: A retrospective cohort study
Nan Jiang, Zhenyuan Chen, Li Liu, Xiaoxv Yin, Heping Yang, Xiangping Tan, Jing Wang, Hui Li, Mengge Tian, Zuxun Lu, Nian Xiong, Yanhong Gong
Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2020.108619
To determine the association between metformin use and mortality and ARDS incidence in patients with COVID-19 and type 2 diabetes. Methods: This study was a multi-center retrospective analysis of COVID-19 patients with type 2 diabetes and admitted to four hospitals in Hubei province, China from December 31st, 2019 to March 31st, 2020. Patients were divided into two groups according to their exposure to metformin during hospitalization. The outcomes of interest were 30-day allcause mortality and incidence of ARDS. We used mixed-effect Cox model and random effect logistic regression to evaluate the associations of metformin use with outcomes, adjusted for baseline characteristics. Results: Of 328 patients with COVID-19 and type 2 diabetes included in the study cohort, 30.5% (100/328) were in the metformin group. In the mixed-effected model, metformin use was associated with the lower incidence of ARDS. There was no significant association between metformin use and 30-day all-cause mortality. Propensity score-matched analysis
Authors' Contributions ZC, NJ, XY, LL, NX, and YG, were responsible for the conception, design, and writing of the manuscript. HY, XT, JW, HL, and MT were responsible for the acquisition of data and literature research. ZC, NJ, XY, LL, ZL were responsible for the analysis and interpretation of data. All authors reviewed and revised the manuscript and approved the final version.
Appendix A. Supplementary material Supplementary data to this article can be found online at https://doi.org/10.1016/j.diabres.2020.108619.
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References
Bode, Garrett, Messler, Mcfarland, Crowe et al., Glycemic characteristics and clinical outcomes of COVID-19 patients hospitalized in the United States, J Diabetes Sci Technol,
doi:10.1177/1932296820924469Bornstein, Rubino, Khunti, Mingrone, Hopkins et al., Practical recommendations for the management of diabetes in patients with COVID-19, Lancet Diabetes Endocrinol,
doi:10.1016/S2213-8587(20)30152-2Bramante, Ingraham, Murray, Marmor, Hoversten et al., Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19,
doi:10.1101/2020.06.19.20135095Cheng, Liu, Li, Zhang, Lei et al., Metformin is associated with higher incidence of acidosis, but not mortality, in individuals with COVID-19 and pre-existing Type 2 diabetes, Cell Metab,
doi:10.1016/j.cmet.2020.08.013Do, Kim, Park, Cho, Kang, Is there an association between metformin use and clinical outcomes in diabetes patients with COVID-19?, Diabetes Metab
Hariyanto, Kurniawan, Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection, Obes Med,
doi:10.1016/j.obmed.2020.100290Hyun, Shin, Lee, Metformin down-regulates TNF-a secretion via suppression of scavenger receptors in macrophages, Immune Netw,
doi:10.4110/in.2013.13.4.123Katulanda, Dissanayake, Ranathunga, Ratnasamy, Wijewickrama et al., Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature, Diabetologia,
doi:10.1007/s00125-020-05164-xKumar, Arora, Sharma, Anikhindi, Bansal et al., Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis, Diabetes Metab Syndr,
doi:10.1016/j.dsx.2020.04.044Luo, Qiu, Liu, Liu, Zheng et al., Metformin treatment was associated with decreased mortality in COVID-19 patients with diabetes in a retrospective analysis, Am J Trop Med Hyg,
doi:10.4269/ajtmh.20-0375Oh, Song, Prior metformin therapy and 30-day mortality in patients with acute respiratory distress syndrome: a nationwide cohort study, Ann Palliat Med,
doi:10.21037/apm.2020.04.25Pe ´rez-Belmonte, Torres-Pen ˜a, Lo ´pez-Carmona, Ayala-Gutie ´rrez, Fuentes-Jime ´nez et al., Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study, BMC Med,
doi:10.1186/s12916-020-01832-2Piwkowska, Rogacka, Jankowski, Dominiczak, Stepin ´ski et al., Metformin induces suppression of NAD(P)H oxidase activity in podocytes, Biochem Biophys Res Commun,
doi:10.1016/j.bbrc.2010.01.119Ranieri, Rubenfeld, Thompson, Ferguson, Caldwell, Acute respiratory distress syndrome: the Berlin Definition, JAMA,
doi:10.1001/jama.2012.5669Roncon, Zuin, Rigatelli, Zuliani, Diabetic patients with COVID-19 infection are at higher risk of ICU admission and poor short-term outcome, J Clin Virol,
doi:10.1016/j.jcv.2020.104354Schuiveling, Vazirpanah, Radstake, Zimmermann, Broen, Metformin, a new era for an old drug in the treatment of immune mediated disease?, Curr Drug Targets,
doi:10.2174/1389450118666170613081730Simonnet, Chetboun, Poissy, Raverdy, Noulette et al., High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation, Silver Spring,
doi:10.1002/oby.22831Who, Coronavirus disease (COVID-9) outbreak situation
Who, Laboratory testing for 2019 novel coronavirus (2019-nCoV) in suspected human cases Interim guidance
Who, WHOTimeline-COVID-19
Wu, Mcgoogan, Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention, JAMA,
doi:10.1001/jama.2020.2648Yan, Yang, Wang, Ren, Zhang et al., Clinical characteristics and outcomes of patients with severe covid-19 with diabetes, BMJ Open Diabetes Res Care,
doi:10.1136/bmjdrc-2020-001343Yang, Zheng, Gou, Pu, Chen et al., Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis, Int J Infect Dis,
doi:10.1016/j.ijid.2020.03.017Zangrillo, Beretta, Scandroglio, Monti, Fominskiy et al., Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy, Crit Care Resusc
Zhang, Liu, Li, Luo, Liu et al., Antiinflammatory effects of matrine in LPS-induced acute lung injury in mice, Eur J Pharm Sci,
doi:10.1016/j.ejps.2011.09.020Zhu, She, Cheng, Qin, Zhang et al., Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes, Cell Metab,
doi:10.1016/j.cmet.2020.04.021
