Metformin alleviates inflammatory response and severity rate of COVID-19 infection in elderly individuals

Chen et al., Translational Medicine of Aging, doi:10.1016/j.tma.2024.04.001, Jun 2024
ICU admission 81% improvement lower risk ← → higher risk Pneumonia 39% Hospitalization time 17% Metformin for COVID-19  Chen et al.  PROPHYLAXIS Is prophylaxis with metformin beneficial for COVID-19? Retrospective 413 patients in China (March - June 2022) Lower ICU admission (p=0.0079) and progression (p=0.0092) c19early.org Chen et al., Translational Medicine of.., Jun 2024 0 0.5 1 1.5 2+ RR
Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020, now with p < 0.00000000001 from 107 studies.
No treatment is 100% effective. Protocols combine treatments.
6,200+ studies for 200+ treatments. c19early.org
Retrospective 413 hospitalized COVID-19 patients with type 2 diabetes in China showing lower ICU admission, lower pneumonia incidence, and shorter hospital stay with metformin use.
Standard of Care (SOC) for COVID-19 in the study country, China, is average with moderate efficacy for approved treatments1.
risk of ICU admission, 80.7% lower, RR 0.19, p = 0.008, treatment 2 of 121 (1.7%), control 25 of 292 (8.6%), NNT 14.
pneumonia, 39.1% lower, RR 0.61, p = 0.009, treatment 25 of 121 (20.7%), control 99 of 292 (33.9%), NNT 7.6.
hospitalization time, 16.6% lower, relative time 0.83, p = 0.001, treatment 121, control 292.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Chen et al., 8 Jun 2024, retrospective, China, peer-reviewed, mean age 66.3, 11 authors, study period 20 March, 2022 - 18 June, 2022. Contact: yj11254@rjh.com.cn, nhhl@sina.com.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org November 2025 China United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR China favored low-cost treatments.The average efficacy of treatments was moderate.Low-cost treatments improve early treatment, andprovide complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org November 2025 China United Kingdom Russia USA Sudan Angola Colombia Kenya Mozambique Pakistan Argentina Vietnam Peru Philippines Spain Brazil Italy France Japan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Côte d'Ivoire Eritrea Togo Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria China favored low-cost treatments.The average efficacy was moderate.Low-cost protocols improve early treatment,and add complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Metformin alleviates inflammatory response and severity rate of COVID-19 infection in elderly individuals
Xuguang Chen, Sheng Huang, Shengyi Shi, Hanwen Sun, Lei Zhou, Heng Wang, Yan Li, Eric Gilson, Yiming Lu, Lan Hu, Jing Ye
Translational Medicine of Aging, doi:10.1016/j.tma.2024.04.001
Highlights • Metformin may reduce the risk of requiring ICU treatment after COVID-19 infection. • The mechanism by which elderly COVID-19 patients benefit from metformin may not be due to blood glucose control, but rather a reduction in inflammatory response and an improvement in immune status. • Metformin has a specific protective function for patients over 60 years old.
Author contributions JY and LH contributed to the conception and design of the study. YM-L gave guidance on design options. XG-C, SH, SY-S, HW-S, LZ organized the database. HW and YL performed the statistical analysis. XG-C and SY-S wrote the first draft of the manuscript. JY, XG-C and EG wrote parts of the manuscript. All authors participated in the revision of the manuscript, read and approved the submitted version. Declaration of competing interest The study was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. Supplementary material Supplementary Tab 1 J o u r n a l P r e -p r o o f
References
Ao, Li, Wei, Clinical and virological characteristics of SARS-CoV-2 Omicron BA
Barzilai, Crandall, Kritchevsky, Metformin as a Tool to Target Aging, J]. Cell metabolism
Camell, Yousefzadeh, Zhu, Senolytics reduce coronavirus-related mortality in old mice, J
Chen, Yang, Cheng, Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication, J]. Diabetes care
Cheng, Xin, Chen, Effects of metformin, insulin on COVID-19 patients with preexisted type 2 diabetes: A multicentral retrospective study, J]. Life sciences
Delval, Hantute-Ghesquier, Sencio, Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters [J], Nature aging
Foretz, Guigas, Viollet, Metformin: update on mechanisms of action and repurposing potential, J]. Nature reviews Endocrinology
Hao, Zhang, Meng, Comparison of different drug for reducing testosterone levels in women with polycystic ovary syndrome: A systematic review and network meta-analysis, J]. Medicine
Ibrahim, Lowe, Bramante, Metformin and Covid-19: Focused Review of Mechanisms and Current Literature Suggesting Benefit, Frontiers in endocrinology
Kahnert, Andreas, Kellerer, Reduced decline of lung diffusing capacity in COPD patients with diabetes and metformin treatment, J]. Sci Rep
Ling, Lu, Liu, The Omicron BA.2.2.1 subvariant drove the wave of SARS-CoV-2 outbreak in Shanghai during spring 2022, J]. Cell discovery
Ma, Patel, Vemparala, Metformin is associated with favorable outcomes in patients with COVID-19 and type 2 diabetes mellitus, J]. Sci Rep
Morales, Morris, Metformin in cancer treatment and prevention, J]. Annual review of medicine
Nguyen, Ho, Nguyen, Preadmission use of antidiabetic medications and J o u r n a l P r e -p r o o f mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis, J]. Metabolism: clinical and experimental
Ojeda-Fernández, Foresta, Macaluso, Metformin use is associated with a decrease in the risk of hospitalization and mortality in COVID-19 patients with diabetes: A population-based study in Lombardy [J], Diabetes, obesity & metabolism
Parish, Swindell, Metformin has heterogeneous effects on model organism lifespans and is beneficial when started at an early age in Caenorhabditis elegans: A systematic review and meta-analysis, J]. Aging cell
Soukas, Hao, Wu, Metformin as Anti-Aging Therapy: Is It for Everyone?, J]. Trends in endocrinology and metabolism: TEM
Ventura-López, Cervantes-Luevano, Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, doubleblind, Phase IIb clinical trial, J]. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Wargny, Potier, Gourdy, Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study, Diabetologia
Xian, Liu, Nilsson, Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation, J]. Immunity
Yen, Wei, Chiu, Cardiovascular outcomes of metformin use in patients with type 2 diabetes and chronic obstructive pulmonary disease [J], Frontiers in pharmacology
Zheng, Xu, Walker, Evaluating the efficacy and mechanism of metformin targets on reducing Alzheimer's disease risk in the general population: a Mendelian randomisation study, Diabetologia
Zhu, Zeng, Liu, Association of Glucose-Lowering Drugs With Outcomes in Patients With Diabetes Before Hospitalization for COVID-19: A Systematic Review and Network Metaanalysis, JAMA network open
DOI record: { "DOI": "10.1016/j.tma.2024.04.001", "ISSN": [ "2468-5011" ], "URL": "http://dx.doi.org/10.1016/j.tma.2024.04.001", "alternative-id": [ "S2468501124000026" ], "assertion": [ { "label": "This article is maintained by", "name": "publisher", "value": "Elsevier" }, { "label": "Article Title", "name": "articletitle", "value": "Metformin alleviates inflammatory response and severity rate of COVID-19 infection in elderly individuals" }, { "label": "Journal Title", "name": "journaltitle", "value": "Translational Medicine of Aging" }, { "label": "CrossRef DOI link to publisher maintained version", "name": "articlelink", "value": "https://doi.org/10.1016/j.tma.2024.04.001" }, { "label": "Content Type", "name": "content_type", "value": "article" }, { "label": "Copyright", "name": "copyright", "value": "© 2024 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd." } ], "author": [ { "ORCID": "http://orcid.org/0000-0001-7361-0959", "affiliation": [], "authenticated-orcid": false, "family": "Chen", "given": "Xuguang", "sequence": "first" }, { "affiliation": [], "family": "Huang", "given": "Sheng", "sequence": "additional" }, { "affiliation": [], "family": "Shi", "given": "Shengyi", "sequence": "additional" }, { "affiliation": [], "family": "Sun", "given": "Hanwen", "sequence": "additional" }, { "affiliation": [], "family": "Zhou", "given": "Lei", "sequence": "additional" }, { "affiliation": [], "family": "Wang", "given": "Heng", "sequence": "additional" }, { "affiliation": [], "family": "Li", "given": "Yan", "sequence": "additional" }, { "affiliation": [], "family": "Gilson", "given": "Eric", "sequence": "additional" }, { "affiliation": [], "family": "Lu", "given": "Yiming", "sequence": "additional" }, { "affiliation": [], "family": "Hu", "given": "Lan", "sequence": "additional" }, { "affiliation": [], "family": "Ye", "given": "Jing", "sequence": "additional" } ], "container-title": "Translational Medicine of Aging", "container-title-short": "Translational Medicine of Aging", "content-domain": { "crossmark-restriction": true, "domain": [ "elsevier.com", "sciencedirect.com" ] }, "created": { "date-parts": [ [ 2024, 6, 9 ] ], "date-time": "2024-06-09T00:11:28Z", "timestamp": 1717891888000 }, "deposited": { "date-parts": [ [ 2024, 6, 9 ] ], "date-time": "2024-06-09T00:11:41Z", "timestamp": 1717891901000 }, "funder": [ { "DOI": "10.13039/501100003395", "doi-asserted-by": "publisher", "name": "Shanghai Municipal Education Commission" }, { "DOI": "10.13039/501100001809", "award": [ "81671900", "82225018", "91749126", "81871549", "81971312", "81911530241" ], "doi-asserted-by": "publisher", "name": "National Natural Science Foundation of China" } ], "indexed": { "date-parts": [ [ 2024, 6, 9 ] ], "date-time": "2024-06-09T01:10:22Z", "timestamp": 1717895422702 }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2024, 6 ] ] }, "language": "en", "license": [ { "URL": "https://www.elsevier.com/tdm/userlicense/1.0/", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 6, 1 ] ], "date-time": "2024-06-01T00:00:00Z", "timestamp": 1717200000000 } }, { "URL": "https://www.elsevier.com/legal/tdmrep-license", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 6, 1 ] ], "date-time": "2024-06-01T00:00:00Z", "timestamp": 1717200000000 } }, { "URL": "http://creativecommons.org/licenses/by-nc-nd/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2024, 4, 18 ] ], "date-time": "2024-04-18T00:00:00Z", "timestamp": 1713398400000 } } ], "link": [ { "URL": "https://api.elsevier.com/content/article/PII:S2468501124000026?httpAccept=text/xml", "content-type": "text/xml", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://api.elsevier.com/content/article/PII:S2468501124000026?httpAccept=text/plain", "content-type": "text/plain", "content-version": "vor", "intended-application": "text-mining" } ], "member": "78", "original-title": [], "prefix": "10.1016", "published": { "date-parts": [ [ 2024, 6 ] ] }, "published-print": { "date-parts": [ [ 2024, 6 ] ] }, "publisher": "Elsevier BV", "reference": [ { "DOI": "10.1038/s41574-023-00833-4", "article-title": "Metformin: update on mechanisms of action and repurposing potential", "author": "Foretz", "doi-asserted-by": "crossref", "first-page": "460", "issue": "8", "journal-title": "Nature reviews Endocrinology", "key": "10.1016/j.tma.2024.04.001_bib1", "volume": "19", "year": "2023" }, { "DOI": "10.1146/annurev-med-062613-093128", "article-title": "Metformin in cancer treatment and prevention", "author": "Morales", "doi-asserted-by": "crossref", "first-page": "17", "journal-title": "Annual review of medicine", "key": "10.1016/j.tma.2024.04.001_bib2", "volume": "66", "year": "2015" }, { "DOI": "10.1007/s00125-022-05743-0", "article-title": "Evaluating the efficacy and mechanism of metformin targets on reducing Alzheimer's disease risk in the general population: a Mendelian randomisation study", "author": "Zheng", "doi-asserted-by": "crossref", "first-page": "1664", "issue": "10", "journal-title": "Diabetologia", "key": "10.1016/j.tma.2024.04.001_bib3", "volume": "65", "year": "2022" }, { "DOI": "10.1111/acel.13733", "article-title": "Metformin has heterogeneous effects on model organism lifespans and is beneficial when started at an early age in Caenorhabditis elegans: A systematic review and meta-analysis", "author": "Parish", "doi-asserted-by": "crossref", "issue": "12", "journal-title": "Aging cell", "key": "10.1016/j.tma.2024.04.001_bib4", "volume": "21", "year": "2022" }, { "DOI": "10.3389/fphar.2022.919881", "article-title": "Cardiovascular outcomes of metformin use in patients with type 2 diabetes and chronic obstructive pulmonary disease", "author": "Yen", "doi-asserted-by": "crossref", "journal-title": "Frontiers in pharmacology", "key": "10.1016/j.tma.2024.04.001_bib5", "volume": "13", "year": "2022" }, { "DOI": "10.1038/s41598-022-05276-x", "article-title": "Reduced decline of lung diffusing capacity in COPD patients with diabetes and metformin treatment", "author": "Kahnert", "doi-asserted-by": "crossref", "first-page": "1435", "issue": "1", "journal-title": "Sci Rep", "key": "10.1016/j.tma.2024.04.001_bib6", "volume": "12", "year": "2022" }, { "DOI": "10.1097/MD.0000000000035152", "article-title": "Comparison of different drug for reducing testosterone levels in women with polycystic ovary syndrome: A systematic review and network meta-analysis", "author": "Hao", "doi-asserted-by": "crossref", "issue": "41", "journal-title": "Medicine", "key": "10.1016/j.tma.2024.04.001_bib7", "volume": "102", "year": "2023" }, { "DOI": "10.1016/j.cmet.2016.05.011", "article-title": "Metformin as a Tool to Target Aging", "author": "Barzilai", "doi-asserted-by": "crossref", "first-page": "1060", "issue": "6", "journal-title": "Cell metabolism", "key": "10.1016/j.tma.2024.04.001_bib8", "volume": "23", "year": "2016" }, { "DOI": "10.1016/j.metabol.2022.155196", "article-title": "Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis", "author": "Nguyen", "doi-asserted-by": "crossref", "journal-title": "Metabolism: clinical and experimental", "key": "10.1016/j.tma.2024.04.001_bib9", "volume": "131", "year": "2022" }, { "DOI": "10.1001/jamanetworkopen.2022.44652", "article-title": "Association of Glucose-Lowering Drugs With Outcomes in Patients With Diabetes Before Hospitalization for COVID-19: A Systematic Review and Network Meta-analysis", "author": "Zhu", "doi-asserted-by": "crossref", "issue": "12", "journal-title": "JAMA network open", "key": "10.1016/j.tma.2024.04.001_bib10", "volume": "5", "year": "2022" }, { "DOI": "10.3389/fendo.2021.587801", "article-title": "Metformin and Covid-19: Focused Review of Mechanisms and Current Literature Suggesting Benefit", "author": "Ibrahim", "doi-asserted-by": "crossref", "journal-title": "Frontiers in endocrinology", "key": "10.1016/j.tma.2024.04.001_bib11", "volume": "12", "year": "2021" }, { "DOI": "10.1038/s41421-022-00468-1", "article-title": "The Omicron BA.2.2.1 subvariant drove the wave of SARS-CoV-2 outbreak in Shanghai during spring 2022", "author": "Ling", "doi-asserted-by": "crossref", "first-page": "97", "issue": "1", "journal-title": "Cell discovery", "key": "10.1016/j.tma.2024.04.001_bib12", "volume": "8", "year": "2022" }, { "DOI": "10.1016/j.jinf.2022.07.027", "article-title": "Clinical and virological characteristics of SARS-CoV-2 Omicron BA.2.2 variant outbreaks during April to May, 2022, Shanghai, China", "author": "Ao", "doi-asserted-by": "crossref", "first-page": "573", "issue": "5", "journal-title": "The Journal of infection", "key": "10.1016/j.tma.2024.04.001_bib13", "volume": "85", "year": "2022" }, { "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", "author": "Wargny", "doi-asserted-by": "crossref", "first-page": "778", "issue": "4", "journal-title": "Diabetologia", "key": "10.1016/j.tma.2024.04.001_bib14", "volume": "64", "year": "2021" }, { "DOI": "10.1016/j.lfs.2021.119371", "article-title": "Effects of metformin, insulin on COVID-19 patients with pre-existed type 2 diabetes: A multicentral retrospective study", "author": "Cheng", "doi-asserted-by": "crossref", "journal-title": "Life sciences", "key": "10.1016/j.tma.2024.04.001_bib15", "volume": "275", "year": "2021" }, { "DOI": "10.1111/dom.14648", "article-title": "Metformin use is associated with a decrease in the risk of hospitalization and mortality in COVID-19 patients with diabetes: A population-based study in Lombardy", "author": "Ojeda-Fernández", "doi-asserted-by": "crossref", "first-page": "891", "issue": "5", "journal-title": "Diabetes, obesity & metabolism", "key": "10.1016/j.tma.2024.04.001_bib16", "volume": "24", "year": "2022" }, { "DOI": "10.1038/s41598-022-09639-2", "article-title": "Metformin is associated with favorable outcomes in patients with COVID-19 and type 2 diabetes mellitus", "author": "Ma", "doi-asserted-by": "crossref", "first-page": "5553", "issue": "1", "journal-title": "Sci Rep", "key": "10.1016/j.tma.2024.04.001_bib17", "volume": "12", "year": "2022" }, { "DOI": "10.1016/j.tem.2019.07.015", "article-title": "Metformin as Anti-Aging Therapy: Is It for Everyone?", "author": "Soukas", "doi-asserted-by": "crossref", "first-page": "745", "issue": "10", "journal-title": "Trends in endocrinology and metabolism: TEM", "key": "10.1016/j.tma.2024.04.001_bib18", "volume": "30", "year": "2019" }, { "DOI": "10.1126/science.abe4832", "article-title": "Senolytics reduce coronavirus-related mortality in old mice", "author": "Camell", "doi-asserted-by": "crossref", "issue": "6552", "journal-title": "Science (New York, NY)", "key": "10.1016/j.tma.2024.04.001_bib19", "volume": "373", "year": "2021" }, { "DOI": "10.1038/s43587-023-00442-w", "article-title": "Removal of senescent cells reduces the viral load and attenuates pulmonary and systemic inflammation in SARS-CoV-2-infected, aged hamsters", "author": "Delval", "doi-asserted-by": "crossref", "first-page": "829", "issue": "7", "journal-title": "Nature aging", "key": "10.1016/j.tma.2024.04.001_bib20", "volume": "3", "year": "2023" }, { "DOI": "10.2337/dc20-0660", "article-title": "Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication", "author": "Chen", "doi-asserted-by": "crossref", "first-page": "1399", "issue": "7", "journal-title": "Diabetes care", "key": "10.1016/j.tma.2024.04.001_bib21", "volume": "43", "year": "2020" }, { "article-title": "Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial", "author": "Ventura-López", "journal-title": "Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie", "key": "10.1016/j.tma.2024.04.001_bib22", "volume": "152", "year": "2022" }, { "DOI": "10.1016/j.immuni.2021.05.004", "article-title": "Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation", "author": "Xian", "doi-asserted-by": "crossref", "issue": "7", "journal-title": "Immunity", "key": "10.1016/j.tma.2024.04.001_bib23", "volume": "54", "year": "2021" } ], "reference-count": 23, "references-count": 23, "relation": {}, "resource": { "primary": { "URL": "https://linkinghub.elsevier.com/retrieve/pii/S2468501124000026" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Metformin alleviates inflammatory response and severity rate of COVID-19 infection in elderly individuals", "type": "journal-article", "update-policy": "http://dx.doi.org/10.1016/elsevier_cm_policy" }
Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.
  or use drag and drop   
Submit