{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:13:35Z","timestamp":1790705615151,"version":"4.1.0"},"reference-count":135,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T00:00:00Z","timestamp":1624320000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008982","name":"Qatar National Research Fund","doi-asserted-by":"publisher","award":["NPRP 11S-1214-170101"],"award-info":[{"award-number":["NPRP 11S-1214-170101"]}],"id":[{"id":"10.13039\/100008982","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Coronavirus Disease 2019 (COVID-19), caused by a new strain of coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared a pandemic by WHO on March 11, 2020. Soon after its emergence in late December 2019, it was noticed that diabetic individuals were at an increased risk of COVID-19\u2013associated complications, ICU admissions, and mortality. Maintaining proper blood glucose levels using insulin and\/or other oral antidiabetic drugs (such as Metformin) reduced the detrimental effects of COVID-19. Interestingly, in diabetic COVID-19 patients, while insulin administration was associated with adverse outcomes, Metformin treatment was correlated with a significant reduction in disease severity and mortality rates among affected individuals. Metformin was extensively studied for its antioxidant, anti-inflammatory, immunomodulatory, and antiviral capabilities that would explain its ability to confer cardiopulmonary and vascular protection in COVID-19. Here, we describe the various possible molecular mechanisms that contribute to Metformin therapy\u2019s beneficial effects and lay out the scientific basis of repurposing Metformin for use in COVID-19 patients.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009634","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T17:22:41Z","timestamp":1624382561000},"page":"e1009634","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":51,"title":["Diabetes and coronavirus (SARS-CoV-2): Molecular mechanism of Metformin intervention and the scientific basis of drug repurposing"],"prefix":"10.1371","volume":"17","author":[{"given":"Elizabeth","family":"Varghese","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5541-6623","authenticated-orcid":true,"given":"Samson Mathews","family":"Samuel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alena","family":"Liskova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4312-5076","authenticated-orcid":true,"given":"Peter","family":"Kubatka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5196-3366","authenticated-orcid":true,"given":"Dietrich","family":"B\u00fcsselberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,22]]},"reference":[{"key":"ppat.1009634.ref001","unstructured":"WHO. Timeline of WHO\u2019s response to COVID-19. 2020 [cited 2021 Feb 10]. Available from: https:\/\/www.who.int\/news-room\/detail\/29-06-2020-covidtimeline."},{"key":"ppat.1009634.ref002","unstructured":"JHU. Coronavirus Resource Center. 2021 [cited 2021 May 16]. Available from: https:\/\/coronavirus.jhu.edu\/."},{"issue":"1","key":"ppat.1009634.ref003","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1186\/s12931-020-01479-w","article-title":"From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses.","volume":"21","author":"Z Zhu","year":"2020","journal-title":"Respir Res."},{"key":"ppat.1009634.ref004","doi-asserted-by":"crossref","DOI":"10.1016\/j.diabres.2020.108268","article-title":"Is metformin ahead in the race as a repurposed host-directed therapy for patients with diabetes and COVID-19?","volume":"165","author":"AK Singh","year":"2020","journal-title":"Diabetes Res Clin Pract"},{"key":"ppat.1009634.ref005","first-page":"2020","article-title":"Effects of hypertension, diabetes and coronary heart disease on COVID-19 diseases severity: a systematic review and meta-analysis.","author":"Y Chen","year":"2020","journal-title":"medRxiv."},{"key":"ppat.1009634.ref006","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.3389\/fphar.2020.01278","article-title":"COVID-19 Usurps Host Regulatory Networks.","volume":"11","author":"CS Curran","year":"2020","journal-title":"Front Pharmacol."},{"issue":"12","key":"ppat.1009634.ref007","doi-asserted-by":"crossref","DOI":"10.3390\/biom9120789","article-title":"Paclitaxel\u2019s Mechanistic and Clinical Effects on Breast Cancer.","volume":"9","author":"TM Abu Samaan","year":"2019","journal-title":"Biomolecules"},{"issue":"9","key":"ppat.1009634.ref008","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/S2213-8587(20)30238-2","article-title":"COVID-19 in people with diabetes: understanding the reasons for worse outcomes","volume":"8","author":"M Apicella","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"issue":"3","key":"ppat.1009634.ref009","doi-asserted-by":"crossref","first-page":"199","DOI":"10.20945\/2359-3997000000256","article-title":"Type 2 diabetes as a major risk factor for COVID-19 severity: a meta-analysis.","volume":"64","author":"LC Pinto","year":"2020","journal-title":"Arch Endocrinol Metab."},{"issue":"3","key":"ppat.1009634.ref010","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/pedi.13013","article-title":"Summary of recommendations regarding COVID-19 in children with diabetes: Keep Calm and Mind your Diabetes Care and Public Health Advice.","volume":"21","author":"ISPAD","year":"2020","journal-title":"Pediatr Diabetes."},{"issue":"11","key":"ppat.1009634.ref011","doi-asserted-by":"crossref","first-page":"e170","DOI":"10.2337\/dc20-1551","article-title":"New-Onset Type 1 Diabetes in Children During COVID-19: Multicenter Regional Findings in the U.K","volume":"43","author":"R Unsworth","year":"2020","journal-title":"Diabetes Care"},{"issue":"4","key":"ppat.1009634.ref012","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1177\/1932296820924469","article-title":"Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Hospitalized in the United States","volume":"14","author":"B Bode","year":"2020","journal-title":"J Diabetes Sci Technol"},{"issue":"6","key":"ppat.1009634.ref013","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":"L Zhu","year":"2020","journal-title":"Cell Metab."},{"issue":"10","key":"ppat.1009634.ref014","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.2337\/dbi20-0022","article-title":"Managing Hyperglycemia in the COVID-19 Inflammatory Storm.","volume":"69","author":"R Gianchandani","year":"2020","journal-title":"Diabetes."},{"key":"ppat.1009634.ref015","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.bcp.2017.03.001","article-title":"Metformin represses glucose starvation induced autophagic response in microvascular endothelial cells and promotes cell death","volume":"132","author":"SM Samuel","year":"2017","journal-title":"Biochem Pharmacol"},{"issue":"11","key":"ppat.1009634.ref016","article-title":"Treatment with a Combination of Metformin and 2-Deoxyglucose Upregulates Thrombospondin-1 in Microvascular Endothelial Cells: Implications in Anti-Angiogenic Cancer Therapy.","volume":"11","author":"SM Samuel","year":"2019","journal-title":"Cancers (Basel)."},{"issue":"12","key":"ppat.1009634.ref017","doi-asserted-by":"crossref","DOI":"10.3390\/biom9120846","article-title":"Metformin: The Answer to Cancer in a Flower? Current Knowledge and Future Prospects of Metformin as an Anti-Cancer Agent in Breast Cancer.","volume":"9","author":"SM Samuel","year":"2019","journal-title":"Biomolecules"},{"issue":"1","key":"ppat.1009634.ref018","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/apha.12644","article-title":"Metformin is not just an antihyperglycaemic drug but also has protective effects on the vascular endothelium","volume":"219","author":"CR Triggle","year":"2017","journal-title":"Acta Physiol (Oxf))."},{"issue":"1","key":"ppat.1009634.ref019","doi-asserted-by":"crossref","DOI":"10.3390\/biom9010016","article-title":"High Glucose Represses the Anti-Proliferative and Pro-Apoptotic Effect of Metformin in Triple Negative Breast Cancer Cells.","volume":"9","author":"S Varghese","year":"2019","journal-title":"Biomolecules"},{"key":"ppat.1009634.ref020","article-title":"Therapeutic Potential of Metformin in COVID-19: Reasoning for its Protective Role","author":"SM 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