{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T07:31:32Z","timestamp":1780817492179,"version":"3.54.1"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","diabetesresearchclinicalpractice.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Research and Clinical Practice"],"published-print":{"date-parts":[[2021,8]]},"DOI":"10.1016\/j.diabres.2021.108977","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T02:03:50Z","timestamp":1626919430000},"page":"108977","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":40,"special_numbering":"C","title":["The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus"],"prefix":"10.1016","volume":"178","author":[{"given":"Wenxing","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10","key":"10.1016\/j.diabres.2021.108977_b0005","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/S2213-8587(20)30271-0","article-title":"Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study","volume":"8","author":"Holman","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"6","key":"10.1016\/j.diabres.2021.108977_b0010","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/j.cmet.2020.04.021","article-title":"Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes","volume":"31","author":"Zhu","year":"2020","journal-title":"Cell Metab"},{"issue":"1","key":"10.1016\/j.diabres.2021.108977_b0015","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41574-020-00435-4","article-title":"COVID-19 and diabetes mellitus: from pathophysiology to clinical management","volume":"17","author":"Lim","year":"2021","journal-title":"Nat Rev Endocrinol"},{"key":"10.1016\/j.diabres.2021.108977_b0020","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.3389\/fphar.2020.01161","article-title":"DPP4 and ACE2 in diabetes and COVID-19: therapeutic targets for cardiovascular complications?","volume":"11","author":"Valencia","year":"2020","journal-title":"Front Pharmacol"},{"key":"10.1016\/j.diabres.2021.108977_b0025","doi-asserted-by":"crossref","first-page":"R211","DOI":"10.1530\/EJE-19-0566","article-title":"Management of endocrine disease: are all GLP-1 agonists equal in the treatment of type 2 diabetes?","volume":"181","author":"Nauck","year":"2019","journal-title":"Eur J Endocrinol"},{"issue":"12","key":"10.1016\/j.diabres.2021.108977_b0030","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1038\/nrneph.2016.159","article-title":"Acute kidney injury from SGLT2 inhibitors: potential mechanisms","volume":"12","author":"Hahn","year":"2016","journal-title":"Nat Rev Nephrol"},{"issue":"1","key":"10.1016\/j.diabres.2021.108977_b0035","doi-asserted-by":"crossref","first-page":"140","DOI":"10.2337\/dc14-2441","article-title":"Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"38","author":"Inzucchi","year":"2015","journal-title":"Diabetes Care"},{"key":"10.1016\/j.diabres.2021.108977_b0040","doi-asserted-by":"crossref","first-page":"b2535","DOI":"10.1136\/bmj.b2535","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"339","author":"Moher","year":"2009","journal-title":"BMJ"},{"issue":"11","key":"10.1016\/j.diabres.2021.108977_b0045","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat Med"},{"key":"10.1016\/j.diabres.2021.108977_b0050","first-page":"719","article-title":"Statistical aspects of the analysis of data from retrospective studies of disease","volume":"22","author":"Mantel","year":"1959","journal-title":"J Natl Cancer Inst"},{"issue":"3","key":"10.1016\/j.diabres.2021.108977_b0055","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Control Clin Trials"},{"issue":"4","key":"10.1016\/j.diabres.2021.108977_b0060","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.2307\/2533446","article-title":"Operating characteristics of a rank correlation test for publication bias","volume":"50","author":"Begg","year":"1994","journal-title":"Biometrics"},{"issue":"8","key":"10.1016\/j.diabres.2021.108977_b0065","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1007\/s00125-020-05180-x","article-title":"Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study","volume":"63","author":"Cariou","year":"2020","journal-title":"Diabetologia"},{"key":"10.1016\/j.diabres.2021.108977_b0070","article-title":"Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19","author":"Bramante","year":"2020","journal-title":"medRxiv"},{"key":"10.1016\/j.diabres.2021.108977_b0075","doi-asserted-by":"crossref","first-page":"101044","DOI":"10.1016\/j.molmet.2020.101044","article-title":"Diabetes, infection risk and COVID-19","volume":"39","author":"Erener","year":"2020","journal-title":"Mol Metab"},{"issue":"6","key":"10.1016\/j.diabres.2021.108977_b0080","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1016\/j.dsx.2020.11.006","article-title":"The effect of metformin consumption on mortality in hospitalized COVID-19 patients: a systematic review and meta-analysis","volume":"14","author":"Lukito","year":"2020","journal-title":"Diabetes Metab Syndr"},{"key":"10.1016\/j.diabres.2021.108977_b0085","first-page":"1","article-title":"Is there a need to reconsider the use of metformin in COVID-19 patients with type 2 diabetes mellitus?","author":"Lazarus","year":"2021","journal-title":"Int J Diabetes Dev Ctries"},{"issue":"1","key":"10.1016\/j.diabres.2021.108977_b0090","doi-asserted-by":"crossref","first-page":"e34","DOI":"10.1016\/S2666-7568(20)30033-7","article-title":"Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis","volume":"2","author":"Bramante","year":"2021","journal-title":"Lancet Healthy Longev"},{"issue":"2","key":"10.1016\/j.diabres.2021.108977_b0095","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.dsx.2021.02.022","article-title":"Metformin is associated with lower hospitalizations, mortality and severe coronavirus infection among elderly medicare minority patients in 8 states in USA","volume":"15","author":"Ghany","year":"2021","journal-title":"Diabetes Metab Syndr"},{"key":"10.1016\/j.diabres.2021.108977_b0100","doi-asserted-by":"crossref","first-page":"108619","DOI":"10.1016\/j.diabres.2020.108619","article-title":"Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: a retrospective cohort study","volume":"173","author":"Jiang","year":"2021","journal-title":"Diabetes Res Clin Pract"},{"issue":"1","key":"10.1016\/j.diabres.2021.108977_b0105","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.jamda.2020.10.031","article-title":"Metformin is associated with decreased 30-day mortality among nursing home residents infected with SARS-CoV2","volume":"22","author":"Lally","year":"2021","journal-title":"J Am Med Dir Assoc"},{"key":"10.1016\/j.diabres.2021.108977_b0110","article-title":"Inpatient use of metformin and acarbose is associated with reduced mortality of COVID-19 patients with type 2 diabetes mellitus","author":"Li","year":"2021","journal-title":"Res Sq"},{"issue":"6","key":"10.1016\/j.diabres.2021.108977_b0115","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/s00592-020-01666-7","article-title":"Metformin use and risk of COVID-19 among patients with type II diabetes mellitus: an NHIS-COVID-19 database cohort study","volume":"58","author":"Oh","year":"2021","journal-title":"Acta Diabetol"},{"issue":"4","key":"10.1016\/j.diabres.2021.108977_b0120","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1007\/s00125-020-05351-w","article-title":"Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study","volume":"64","author":"Wargny","year":"2021","journal-title":"Diabetologia"},{"key":"10.1016\/j.diabres.2021.108977_b0125","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.31268","article-title":"Metformin extends C. elegans lifespan through lysosomal pathway","volume":"6","author":"Chen","year":"2017","journal-title":"Elife"},{"issue":"1-3","key":"10.1016\/j.diabres.2021.108977_b0130","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ejphar.2013.02.038","article-title":"Metformin and cancer","volume":"705","author":"Rizos","year":"2013","journal-title":"Eur J Pharmacol"},{"issue":"4","key":"10.1016\/j.diabres.2021.108977_b0135","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.pbb.2012.03.002","article-title":"Metformin attenuates Alzheimer's disease-like neuropathology in obese, leptin-resistant mice","volume":"101","author":"Li","year":"2012","journal-title":"Pharmacol Biochem Behav"},{"issue":"24","key":"10.1016\/j.diabres.2021.108977_b0140","doi-asserted-by":"crossref","first-page":"E2501","DOI":"10.1073\/pnas.1321776111","article-title":"Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2","volume":"111","author":"De Haes","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"10.1016\/j.diabres.2021.108977_b0145","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.cmet.2016.09.003","article-title":"Metformin activates AMPK through the lysosomal pathway","volume":"24","author":"Zhang","year":"2016","journal-title":"Cell Metab"},{"issue":"7","key":"10.1016\/j.diabres.2021.108977_b0150","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1038\/nm.4345","article-title":"Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug","volume":"23","author":"Wu","year":"2017","journal-title":"Nat Med"},{"issue":"6","key":"10.1016\/j.diabres.2021.108977_b0155","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.cell.2019.08.003","article-title":"Host-microbe-drug-nutrient screen identifies bacterial effectors of metformin therapy","volume":"178","author":"Pryor","year":"2019","journal-title":"Cell"},{"issue":"8","key":"10.1016\/j.diabres.2021.108977_b0160","doi-asserted-by":"crossref","first-page":"945","DOI":"10.2174\/1389450118666170613081730","article-title":"Metformin, a new era for an old drug in the treatment of immune mediated disease?","volume":"19","author":"Schuiveling","year":"2018","journal-title":"Curr Drug Targets"},{"key":"10.1016\/j.diabres.2021.108977_b0165","doi-asserted-by":"crossref","first-page":"108230","DOI":"10.1016\/j.diabres.2020.108230","article-title":"Metformin, neutrophils and COVID-19 infection","volume":"164","author":"Dalan","year":"2020","journal-title":"Diabetes Res Clin Pract"},{"issue":"7","key":"10.1016\/j.diabres.2021.108977_b0170","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.2337\/dc20-0660","article-title":"Clinical characteristics and outcomes of patients with diabetes and COVID-19 in association with glucose-lowering medication","volume":"43","author":"Chen","year":"2020","journal-title":"Diabetes Care"},{"issue":"4","key":"10.1016\/j.diabres.2021.108977_b0175","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.cmet.2020.08.013","article-title":"Metformin is associated with higher incidence of acidosis, but not mortality, in individuals with COVID-19 and pre-existing type 2 diabetes","volume":"32","author":"Cheng","year":"2020","journal-title":"Cell Metab"},{"key":"10.1016\/j.diabres.2021.108977_b0180","article-title":"Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19","volume":"47","author":"Lalau","year":"2020","journal-title":"Diabetes Metab"},{"issue":"4","key":"10.1016\/j.diabres.2021.108977_b0185","doi-asserted-by":"crossref","first-page":"602","DOI":"10.4093\/dmj.2020.0146","article-title":"The clinical characteristics and outcomes of patients with moderate-to-severe coronavirus disease 2019 infection and diabetes in Daegu, South Korea","volume":"44","author":"Kim","year":"2020","journal-title":"Diabetes Metab J"},{"issue":"1","key":"10.1016\/j.diabres.2021.108977_b0190","doi-asserted-by":"crossref","DOI":"10.1186\/s12916-020-01832-2","article-title":"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","volume":"18","author":"P\u00e9rez-Belmonte","year":"2020","journal-title":"BMC Med"},{"key":"10.1016\/j.diabres.2021.108977_b0195","doi-asserted-by":"crossref","DOI":"10.1017\/S0950268820002472","article-title":"Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study","volume":"148","author":"Goodall","year":"2020","journal-title":"Epidemiol Infect"},{"key":"10.1016\/j.diabres.2021.108977_b0200","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4269\/ajtmh.20-0375","article-title":"Metformin treatment was associated with decreased mortality in COVID-19 patients with diabetes in a retrospective analysis","volume":"103","author":"Luo","year":"2020","journal-title":"Am J Trop Med Hyg"},{"issue":"10","key":"10.1016\/j.diabres.2021.108977_b0205","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.4158\/EP-2020-0466","article-title":"Metformin use in diabetes prior to hospitalization: effects on mortality in Covid-19","volume":"26","author":"Li","year":"2020","journal-title":"Endocr Pract"},{"key":"10.1016\/j.diabres.2021.108977_b0210","doi-asserted-by":"crossref","unstructured":"Crouse A, Grimes T, Li P, Might M, Ovalle F, Shalev A. metformin use is associated with reduced mortality in a diverse population with COVID-19 and diabetes. medRxiv. 2020.","DOI":"10.1101\/2020.07.29.20164020"},{"key":"10.1016\/j.diabres.2021.108977_b0215","article-title":"Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy","author":"Zangrillo","year":"2020","journal-title":"Crit Care Resusc"},{"issue":"6","key":"10.1016\/j.diabres.2021.108977_b0220","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1111\/cts.12897","article-title":"Risk of metformin in patients with type 2 diabetes with COVID-19: a preliminary retrospective report","volume":"13","author":"Gao","year":"2020","journal-title":"Clin Transl Sci"}],"container-title":["Diabetes Research and Clinical Practice"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168822721003363?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168822721003363?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T19:18:45Z","timestamp":1759173525000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168822721003363"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8]]},"references-count":44,"alternative-id":["S0168822721003363"],"URL":"https:\/\/doi.org\/10.1016\/j.diabres.2021.108977","relation":{},"ISSN":["0168-8227"],"issn-type":[{"value":"0168-8227","type":"print"}],"subject":[],"published":{"date-parts":[[2021,8]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus","name":"articletitle","label":"Article Title"},{"value":"Diabetes Research and Clinical Practice","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.diabres.2021.108977","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"108977"}}