Conv. Plasma
Nigella Sativa

All metformin studies
Meta analysis
study COVID-19 treatment researchMetforminMetformin (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ ICU admission, both cohor.. 37% Improvement Relative Risk ICU admission, cohort 1 43% ICU admission, cohort 2 31% Metformin for COVID-19  Miguel et al.  Prophylaxis Is prophylaxis with metformin beneficial for COVID-19? Retrospective 132 patients in Spain (March - June 2020) Lower ICU admission with metformin (not stat. sig., p=0.24) Miguel et al., Redox Biology, November 2023 Favors metformin Favors control

Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney

Miguel et al., Redox Biology, doi:10.1016/j.redox.2023.102957
Nov 2023  
  Source   PDF   All   Meta
Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
*, now known with p < 0.00000000001 from 84 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
3,800+ studies for 60+ treatments.
Mouse models showing reduced lung and kidney injury with metformin. Metformin minimized lung damage and fibrosis in a mouse model of LPS-induced ARDS, and reduced UUO and FAN-induced kidney fibrosis. In Vitro study showing that metformin increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis, and inflammation markers in lung epithelial cells.
Authors also include a retrospective study showing lower ICU admission with metformin without statistical significance.
6 preclinical studies support the efficacy of metformin for COVID-19:
A systematic review and meta-analysis of 15 non-COVID-19 preclinical studies showed that metformin inhibits pulmonary inflammation and oxidative stress, minimizes lung injury, and improves survival in animal models of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) Wang. Metformin inhibits SARS-CoV-2 in vitro Parthasarathy, Ventura-López, minimizes LPS-induced cytokine storm in a mouse model Taher, minimizes lung damage and fibrosis in a mouse model of LPS-induced ARDS Miguel, may protect against SARS-CoV-2-induced neurological disorders Yang, may be beneficial via inhibitory effects on ORF3a-mediated inflammasome activation Zhang, reduces UUO and FAN-induced kidney fibrosis Miguel, increases mitochondrial function and decreases TGF-β-induced fibrosis, apoptosis, and inflammation markers in lung epithelial cells Miguel, and may improve outcomes via modulation of immune responses with increased anti-inflammatory T lymphocyte gene expression and via enhanced gut microbiota diversity Petakh.
risk of ICU admission, 37.4% lower, RR 0.63, p = 0.24, treatment 49, control 40, both cohorts combined.
risk of ICU admission, 42.9% lower, RR 0.57, p = 0.34, treatment 3 of 15 (20.0%), control 14 of 40 (35.0%), NNT 6.7.
risk of ICU admission, 31.4% lower, RR 0.69, p = 0.52, treatment 6 of 49 (12.2%), control 5 of 28 (17.9%), NNT 18.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Miguel et al., 17 Nov 2023, retrospective, Spain, peer-reviewed, 19 authors, study period March 2020 - June 2020. Contact:,
This PaperMetforminAll
Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney
Verónica Miguel, Carlos Rey-Serra, Jessica Tituaña, Belén Sirera, Elena Alcalde-Estévez, J Ignacio Herrero, Irene Ranz, Laura Fernández, Carolina Castillo, Lucía Sevilla, James Nagai, Katharina C Reimer, Jitske Jansen, Rafael Kramann, Ivan G Costa, Ana Castro, David Sancho, José Miguel Rodríguez González-Moro, Santiago Lamas
Redox Biology, doi:10.1016/j.redox.2023.102957
Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response, metabolic derangement and ultimate tissue scarring. A positive balance of cellular energy may result crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in cellular energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs metformin (AMPK activator) and baicalin (CPT1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID-19 patients that had been previously treated with metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ ACC signaling increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two indole derivatives, IND6 and IND8 with AMPK activating capacity. Consistently, a reduced time of hospitalization and need of intensive care was observed in COVID-19 patients previously exposed to metformin. Baicalin also mitigated the activation of pro-inflammatory bone marrow-derived macrophages (BMDMs) and reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19. In human epithelial lung and kidney cells, both drugs improved mitochondrial function and prevented TGF-β-induced renal epithelial cell dedifferentiation. Our results support that favoring cellular energy production through enhanced FAO may prove useful in the prevention of COVID-19-induced lung and renal damage.
Author contributions SL conceived and directed research. VM designed, performed and analyzed the majority of experiments. CRS, JT, BS, EA, IR and LF performed experiments. JIH provided technical assistance for mouse experiments. CC performed histological evaluation. KCR, JJ, RK and DS provided intellectual insight and resources. LS and JMRGM collected information about COVID-19 patient cohorts. JN and IC performed bioinformatic studies. AC provided indol-based compounds. All authors helped with the discussion of the results and SL and VM wrote the manuscript. Declaration of competing interest The authors have no conflicts of interest. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi. org/10.1016/j.redox.2023.102957.
Ayres, A metabolic handbook for the COVID-19 pandemic, Nat. Metab
Berber, Sumbria, Kokkaya, A metabolic blueprint of COVID-19 and longterm vaccine efficacy, Drug Metab Pers Ther
Berlin, Gulick, Martinez, Severe covid-19, N. Engl. J. Med
Bramante, Buse, Liebovitz, Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial, Lancet Infect. Dis
Carling, AMPK signalling in health and disease, Curr. Opin. Cell Biol
Chevalier, Forbes, Thornhill, Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy, Kidney Int
Console, Scalise, Giangregorio, The link between the mitochondrial fatty acid oxidation derangement and kidney injury, Front. Physiol
Cui, Xie, Banerjee, Impairment of fatty acid oxidation in alveolar epithelial cells mediates acute lung injury, Am. J. Respir. Cell Mol. Biol
Dai, Liang, Zhao, Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis, Proc. Natl. Acad. Sci. U. S. A
De Boer, Petrache, Goldstein, Decreased fatty acid oxidation and altered lactate production during exercise in patients with post-acute COVID-19 syndrome, Am. J. Respir. Crit. Care Med
Erickson, Fenno, Barzilai, Metformin for treatment of acute COVID-19: systematic review of clinical trial data against SARS-CoV-2, Diabetes Care
Fajgenbaum, June, Cytokine storm, N. Engl. J. Med
Fink, Henry, Tange, Experimental folic acid nephropathy, Pathology
Foretz, Guigas, Bertrand, Metformin: from mechanisms of action to therapies, Cell Metabol
Grant, Morales-Nebreda, Markov, Circuits between infected macrophages and T cells in SARS-CoV-2 pneumonia, Nature
He, Wondisford, Metformin action: concentrations matter, Cell Metabol
Huynh, Green, Koves, Measurement of fatty acid oxidation rates in animal tissues and cell lines, Methods Enzymol
Jackson, Farzan, Chen, Mechanisms of SARS-CoV-2 entry into cells, Nat. Rev. Mol. Cell Biol
Jansen, Reimer, Nagai, SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids, Cell Stem Cell
Jung, Park, Huh, The effect of human adipose-derived stem cells on lipopolysaccharide-induced acute respiratory distress syndrome in mice, Ann. Transl. Med
Kang, Ahn, Choi, Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development, Nat. Med
Kheirollahi, Wasnick, Biasin, Metformin induces lipogenic differentiation in myofibroblasts to reverse lung fibrosis, Nat. Commun
Kulkarni, Gubbi, Barzilai, Benefits of metformin in attenuating the hallmarks of aging, Cell Metabol
Lee, Su, Baloni, Integrated analysis of plasma and single immune cells uncovers metabolic changes in individuals with COVID-19, Nat. Biotechnol
Li, Yang, Yan, Metformin in patients with COVID-19: a systematic review and meta-analysis, Front. Med
Lin, Tsai, Hsu, Study of baicalin toward COVID-19 treatment: in silico target analysis and in vitro inhibitory effects on SARS-CoV-2 proteases, Biomed. Hub
Livak, Schmittgen, Analysis of relative gene expression data using realtime quantitative PCR and the 2(-Delta Delta C(T)) Method, Methods
Ma, Tian, Zhang, Low-dose metformin targets the lysosomal AMPK pathway through PEN2, Nature
Matheson, Lehner, How does SARS-CoV-2 cause COVID-19?, Science
Merad, Blish, Sallusto, The immunology and immunopathology of COVID-19, Science
Miguel, Tituana, Herrero, Renal tubule Cpt1a overexpression protects from kidney fibrosis by restoring mitochondrial homeostasis, J. Clin. Invest
Moolamalla, Balasubramanian, Chauhan, Host metabolic reprogramming in response to SARS-CoV-2 infection: a systems biology approach, Microb. Pathog
Mora, Bueno, Rojas, Mitochondria in the spotlight of aging and idiopathic pulmonary fibrosis, J. Clin. Invest
Pernicova, Korbonits, Metformin-mode of action and clinical implications for diabetes and cancer, Nat. Rev. Endocrinol
Prasun, COVID-19: a mitochondrial perspective, DNA Cell Biol
Price, Miguel, Ding, Genetic deficiency or pharmacological inhibition of miR-33 protects from kidney fibrosis, JCI Insight
Rangarajan, Bone, Zmijewska, Metformin reverses established lung fibrosis in a bleomycin model, Nat. Med
Ravi, Chacko, Kramer, Defining the effects of storage on platelet bioenergetics: the role of increased proton leak, Biochim. Biophys. Acta
Reddel, Ke, Gerwin, Transformation of human bronchial epithelial cells by infection with SV40 or adenovirus-12 SV40 hybrid virus, or transfection via strontium phosphate coprecipitation with a plasmid containing SV40 early region genes, Cancer Res
Rena, Hardie, Pearson, The mechanisms of action of metformin, Diabetologia
Roberts, Muelas, Taylor, Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome, Metabolomics
Sanchez-Cerrillo, Landete, Aldave, COVID-19 severity associates with pulmonary redistribution of CD1c+ DCs and inflammatory transitional and nonclassical monocytes, J. Clin. Invest
Sanz-Gomez, Aledavood, Beroiz-Salaverri, Novel indolic AMPK modulators induce vasodilatation through activation of the AMPK-eNOS-NO pathway, Sci. Rep
Saz-Leal, Del Fresno, Brandi, Targeting SHIP-1 in myeloid cells enhances trained immunity and boosts response to infection, Cell Rep
Tanner, Alfieri, The fatty acid lipid metabolism nexus in COVID-19, Viruses
Thomas, Stefanoni, Reisz, COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status, JCI Insight
Thompson, Chambers, Liu, Acute respiratory distress syndrome, N. Engl. J. Med
Tian, Xiong, Liu, Pathological study of the 2019 novel coronavirus disease (COVID-19) through postmortem core biopsies, Mod. Pathol
Valdes, Moreno, Rello, Metabolomics study of COVID-19 patients in four different clinical stages, Sci. Rep
Van Der Windt, Chang, Pearce, Measuring bioenergetics in T cells using a Seahorse extracellular Flux analyzer, Curr. Protoc. Im
Varga, Brenner, Phan, Fibrosis Research: Methods and Protocols
Vernooy, Dentener, Van Suylen, Long-term intratracheal lipopolysaccharide exposure in mice results in chronic lung inflammation and persistent pathology, Am. J. Respir. Cell Mol. Biol
Wang, An, Liu, Metformin improves mitochondrial respiratory activity through activation of AMPK, Cell Rep
Wang, Jiang, Zhang, Baicalin protects against renal interstitial fibrosis in mice by inhibiting the TGF-beta/Smad signalling pathway, Pharm. Biol
Wang, Tang, Liu, The role of IL-6 in coronavirus, especially in COVID-19, Front. Pharmacol
Wiernsperger, Al-Salameh, Cariou, Protection by metformin against severe Covid-19: an in-depth mechanistic analysis, Diabetes Metab
Zhou, Myers, Li, Role of AMP-activated protein kinase in mechanism of metformin action, J. Clin. Invest
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. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, 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.
  or use drag and drop