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0 0.5 1 1.5 2+ Oxygen time 44% Improvement Relative Risk Hospitalization time 10% Time to viral- 41% Metformin  Ventura-López et al.  LATE TREATMENT  DB RCT Is late treatment with metformin beneficial for COVID-19? Double-blind RCT 20 patients in Mexico (January 2020 - August 2021) Lower need for oxygen therapy (p=0.03) and faster viral clearance (p=0.029) Ventura-López et al., Biomedicine &amp.., Aug 2022 Favors metformin Favors control

Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial

Ventura-López et al., Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2022.113223
Aug 2022  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
*, now known with p < 0.00000000001 from 87 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,000+ studies for 60+ treatments.
RCT 20 hospitalized COVID-19 patients showing faster viral load reduction and lower oxygen use with metformin glycinate 620mg twice daily for 14 days compared to placebo. The in vitro portion demonstrated inhibition of viral replication and cytopathic effects with metformin glycinate pretreatment.
7 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.
oxygen time, 44.3% lower, relative time 0.56, p = 0.03, treatment mean 5.9 (±4.6) n=10, control mean 10.6 (±6.2) n=10.
hospitalization time, 10.2% lower, relative time 0.90, p = 0.35, treatment mean 8.8 (±6.1) n=10, control mean 9.8 (±5.4) n=10.
time to viral-, 41.1% lower, relative time 0.59, p = 0.03, treatment mean 3.3 (±2.16) n=10, control mean 5.6 (±0.89) n=10.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Ventura-López et al., 31 Aug 2022, Double Blind Randomized Controlled Trial, placebo-controlled, Mexico, peer-reviewed, mean age 47.5, 14 authors, study period January 2020 - August 2021. Contact:,,,,,,,,,,,,,
This PaperMetforminAll
Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial
Claudia Ventura-López, Karla Cervantes-Luevano, Janet S Aguirre-Sánchez, Juan C Flores-Caballero, Carolina Alvarez-Delgado, Johanna Bernaldez-Sarabia, Noemí Sánchez-Campos, Laura A Lugo-Sánchez, Ileana C Rodríguez-Vázquez, Jose G Sander-Padilla, Yulia Romero-Antonio, María M Arguedas-Núñez, Jorge González-Canudas, Alexei F Licea-Navarro
Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2022.113223
The health crisis caused by the new coronavirus SARS-CoV-2 highlights the need to identify new treatment strategies for this viral infection. During the past year, over 400 coronavirus disease (COVID-19) treatment patents have been registered; nevertheless, the presence of new virus variants has triggered more severe disease presentations and reduced treatment effectiveness, highlighting the need for new treatment options for the COVID-19. This study evaluates the Metformin Glycinate (MG) effect on the SARS-CoV-2 in vitro and in vivo viral load. The in vitro study was conducted in a model of Vero E6 cells, while the in vivo study was an adaptive, twoarmed, randomized, prospective, longitudinal, double-blind, multicentric, and phase IIb clinical trial. Our in vitro results revealed that MG effectively inhibits viral replication after 48 h of exposure to the drug, with no cytotoxic effect in doses up to 100 µM. The effect of the MG was also tested against three variants of interest (alpha, delta, and epsilon), showing increased survival rates in cells treated with MG. These results are aligned with our clinical data, which indicates that MG treatment reduces SARS-CoV2-infected patients´viral load in just 3.3 days and supplementary oxygen requirements compared with the control group. We expect our results can guide efforts to position MG as a therapeutic option for COVID-19 patients.
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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Late treatment
is less effective
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