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Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review

Plowman et al., International Journal of Molecular Sciences, doi:10.3390/ijms25105190
May 2024  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
 
*, now known with p < 0.00000000001 from 89 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19early.org
Review of the potential of metformin for preventing inflammatory complications and infectious diseases including COVID-19. Authors discuss evidence from preclinical and clinical studies suggesting metformin may help prevent symptoms of COVID-19 when used alone or as an adjuvant with other antiviral medications. Metformin has been shown to phosphorylate the ACE2 receptor and change its conformation, potentially blocking SARS-CoV-2 binding. It may also control the COVID-19-induced cytokine storm by preventing NF-κB-induced inflammatory response and NLRP3-induced innate immune response in an AMPK-dependent manner. Additionally, by activating endosomal ATPases, metformin could interfere with viral maturation and assembly. Metformin's ability to increase insulin sensitivity and endothelial function may help protect against COVID-19 cardiopulmonary effects.
Reviews covering metformin for COVID-19 include De Jesús-González, Halma, Petakh, Plowman, Tseng, Zhang.
Plowman et al., 10 May 2024, multiple countries, peer-reviewed, 6 authors. Contact: karamana@noordacom.org (corresponding author).
This PaperMetforminAll
Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review
Trevor J Plowman, Hannah Christensen, Myia Aiges, Emely Fernandez, Mujtaba H Shah, Kota V Ramana
International Journal of Molecular Sciences, doi:10.3390/ijms25105190
Metformin, a widely used first-line anti-diabetic therapy for the treatment of type-2 diabetes, has been shown to lower hyperglycemia levels in the blood by enhancing insulin actions. For several decades this drug has been used globally to successfully control hyperglycemia. Lactic acidosis has been shown to be a major adverse effect of metformin in some type-2 diabetic patients, but several studies suggest that it is a typically well-tolerated and safe drug in most patients. Further, recent studies also indicate its potential to reduce the symptoms associated with various inflammatory complications and infectious diseases including coronavirus disease 2019 . These studies suggest that besides diabetes, metformin could be used as an adjuvant drug to control inflammatory and infectious diseases. In this article, we discuss the current understanding of the role of the antidiabetic drug metformin in the prevention of various inflammatory complications and infectious diseases in both diabetics and non-diabetics.
Author Contributions: T.J.P., H.C., M.A., E.F. and M.H.S. drafted the initial manuscript and reviewed and edited the final draft. K.V.R. conceptualized, drafted, reviewed, and edited the manuscript. All authors have read and agreed to the published version of the manuscript.
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In this article, we discuss the current understanding of the role of the ' 'anti-diabetic drug metformin in the prevention of various inflammatory complications and ' 'infectious diseases in both diabetics and non-diabetics.</jats:p>', 'alternative-id': ['ijms25105190'], 'author': [ { 'affiliation': [ { 'name': 'Department of Biomedical Sciences, Noorda College of Osteopathic ' 'Medicine, Provo, UT 84606, USA'}], 'family': 'Plowman', 'given': 'Trevor J.', 'sequence': 'first'}, { 'affiliation': [ { 'name': 'Department of Biomedical Sciences, Noorda College of Osteopathic ' 'Medicine, Provo, UT 84606, USA'}], 'family': 'Christensen', 'given': 'Hannah', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Department of Biomedical Sciences, Noorda College of Osteopathic ' 'Medicine, Provo, UT 84606, USA'}], 'family': 'Aiges', 'given': 'Myia', 'sequence': 'additional'}, { 'affiliation': [ { 'name': 'Department of Biomedical Sciences, Noorda College of Osteopathic ' 'Medicine, Provo, UT 84606, USA'}], 'family': 'Fernandez', 'given': 'Emely', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0002-2442-4874', 'affiliation': [ { 'name': 'Department of Biomedical Sciences, Noorda College of Osteopathic ' 'Medicine, Provo, UT 84606, USA'}], 'authenticated-orcid': False, 'family': 'Shah', 'given': 'Mujtaba H.', 'sequence': 'additional'}, { 'ORCID': 'http://orcid.org/0000-0001-6502-7800', 'affiliation': [ { 'name': 'Department of Biomedical Sciences, Noorda College of Osteopathic ' 'Medicine, Provo, UT 84606, USA'}], 'authenticated-orcid': False, 'family': 'Ramana', 'given': 'Kota V.', 'sequence': 'additional'}], 'container-title': 'International Journal of Molecular Sciences', 'container-title-short': 'IJMS', 'content-domain': {'crossmark-restriction': False, 'domain': []}, 'created': {'date-parts': [[2024, 5, 10]], 'date-time': '2024-05-10T07:21:04Z', 'timestamp': 1715325664000}, 'deposited': { 'date-parts': [[2024, 5, 10]], 'date-time': '2024-05-10T07:43:02Z', 'timestamp': 1715326982000}, 'indexed': {'date-parts': [[2024, 5, 11]], 'date-time': '2024-05-11T00:22:26Z', 'timestamp': 1715386946256}, 'is-referenced-by-count': 0, 'issue': '10', 'issued': {'date-parts': [[2024, 5, 10]]}, 'journal-issue': {'issue': '10', 'published-online': {'date-parts': [[2024, 5]]}}, 'language': 'en', 'license': [ { 'URL': 'https://creativecommons.org/licenses/by/4.0/', 'content-version': 'vor', 'delay-in-days': 0, 'start': { 'date-parts': [[2024, 5, 10]], 'date-time': '2024-05-10T00:00:00Z', 'timestamp': 1715299200000}}], 'link': [ { 'URL': 'https://www.mdpi.com/1422-0067/25/10/5190/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'member': '1968', 'original-title': [], 'page': '5190', 'prefix': '10.3390', 'published': {'date-parts': [[2024, 5, 10]]}, 'published-online': {'date-parts': [[2024, 5, 10]]}, 'publisher': 'MDPI AG', 'reference': [ { 'DOI': '10.3390/ph13120427', 'doi-asserted-by': 'crossref', 'key': 'ref_1', 'unstructured': 'Ahmad, E., Sargeant, J.A., Zaccardi, F., Khunti, K., Webb, D.R., and ' 'Davies, M.J. 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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ 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. FLCCC and WCH provide treatment protocols.
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