Metformin reduces COVID-19 risk: real-time meta analysis of 105 studies

Covid Analysis, May 2025

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https://c19early.org/camfmeta.html

Metformin for COVID-19

3rd treatment shown to reduce risk in July 2020, now with p < 0.00000000001 from 105 studies.

Lower risk for mortality, ventilation, ICU, hospitalization, progression, and recovery.

No treatment is 100% effective. Protocols combine treatments.

5,700+ studies for 135 treatments. c19early.org

Significantly lower risk is seen for mortality, ventilation, ICU admission, hospitalization, progression, and recovery. 69 studies from 63 independent teams in 22 countries show significant benefit.

Meta analysis using the most serious outcome reported shows 31% [27‑34%] lower risk. Results are similar for Randomized Controlled Trials, higher quality studies, and peer-reviewed studies.

Results are very robust — in exclusion sensitivity analysis 83 of 105 studies must be excluded to avoid finding statistically significant efficacy in pooled analysis.

Most studies analyze existing use with diabetic patients. Prophylaxis results typically include continuing use after infection and hospitalization, and greater benefit is seen for more serious outcomes. The TOGETHER RCT shows 27% lower mortality. While not statistically significant, p = 0.53, this is consistent with the mortality results from all studies, 37% [33‑41%].

No treatment is 100% effective. Protocols combine safe and effective options with individual risk/benefit analysis and monitoring. Other treatments are more effective. All data and sources to reproduce this analysis are in the appendix.

23 other meta analyses show significant improvements with metformin for mortality1-22, hospitalization7,13, progression1, and severity8,9,13.

23 meta analyses show significant improvements with metformin for mortality1-22, hospitalization7,13, progression1, and severity8,9,13.

Important missing comments or errors? Let us know.

1. Yang et al., The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus, Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2021.108977.sciencedirect.com, doi.org.

2. Lukito et al., The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2020.11.006.sciencedirect.com, doi.org.

3. Kow et al., Mortality risk with preadmission metformin use in patients with COVID-19 and diabetes: A meta-analysis, Journal of Medical Virology, doi:10.1002/jmv.26498.wiley.com, doi.org.

4. Hariyanto et al., Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection, Obesity Medicine, doi:10.1016/j.obmed.2020.100290.sciencedirect.com, doi.org.

5. Ma et al., Is metformin use associated with low mortality in patients with type 2 diabetes mellitus hospitalized for COVID-19? a multivariable and propensity score-adjusted meta-analysis, PLOS ONE, doi:10.1371/journal.pone.0282210.plos.org, doi.org.

6. Parveen et al., Association of Metformin with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis, Annals of the National Academy of Medical Sciences (India), doi:10.1055/s-0042-1760353.thieme-connect.de, doi.org.

7. Li et al., Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis, Frontiers in Medicine, doi:10.3389/fmed.2021.704666.frontiersin.org, doi.org.

8. Schlesinger et al., Risk phenotypes of diabetes and association with COVID-19 severity and death: an update of a living systematic review and meta-analysis, Diabetologia, doi:10.1007/s00125-023-05928-1.springer.com, doi.org.

9. Petrelli et al., Metformin and Covid-19: a systematic review of systematic reviews with meta-analysis, Acta Biomedica Atenei Parmensis, doi:10.23750/abm.v94iS3.14405.doi.org, doi.org.

10. Oscanoa et al., Metformin therapy and severity and mortality of SARS-CoV-2 infection: a meta-analysis, Clinical Diabetology, doi:10.5603/DK.a2021.0035.viamedica.pl, doi.org.

11. Kan et al., Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis, Frontiers in Endocrinology, doi:10.3389/fendo.2021.708494.frontiersin.org, doi.org.

12. Poly et al., Metformin Use Is Associated with Decreased Mortality in COVID-19 Patients with Diabetes: Evidence from Retrospective Studies and Biological Mechanism, Journal of Clinical Medicine, doi:10.3390/jcm10163507.mdpi.com, doi.org.

13. Song et al., The Effect of Antihyperglycemic Medications on COVID-19: A Meta-analysis and Systematic Review from Observational Studies, Therapeutic Innovation & Regulatory Science, doi:10.1007/s43441-024-00633-6.springer.com, doi.org.

14. Ganesh et al., Does metformin affect outcomes in COVID‐19 patients with new or pre‐existing diabetes mellitus? A systematic review and meta‐analysis, British Journal of Clinical Pharmacology, doi:10.1111/bcp.15258.wiley.com, doi.org.

15. Nassar et al., Noninsulin‐based antihyperglycemic medications in patients with diabetes and COVID‐19: A systematic review and meta‐analysis, Journal of Diabetes, doi:10.1111/1753-0407.13359.wiley.com, doi.org.

16. Zhan et al., Effect of Antidiabetic Therapy on Clinical Outcomes of COVID-19 Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis, Annals of Pharmacotherapy, doi:10.1177/10600280221133577.sagepub.com, doi.org.

17. Nguyen et al., Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis, Metabolism, doi:10.1016/j.metabol.2022.155196.sciencedirect.com, doi.org.

18. Han et al., Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis, Archives of Medical Research, doi:10.1016/j.arcmed.2021.08.002.sciencedirect.com, doi.org.

19. Chen et al., The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis, Frontiers in Endocrinology, doi:10.3389/fendo.2022.895458.frontiersin.org, doi.org.

20. Scheen, A., Metformin and COVID-19: From cellular mechanisms to reduced mortality, Diabetes & Metabolism, doi:10.1016/j.diabet.2020.07.006.sciencedirect.com, doi.org.

21. Sun et al., Is Metformin Use Associated With a Decreased Mortality for COVID-19 Diabetic Patients? A Meta-Analysis, Journal of the Endocrine Society, doi:10.1210/jendso/bvab048.709.oup.com, doi.org.

22. Keels et al., Antidiabetic agent use and clinical outcomes in patients with diabetes hospitalized for COVID-19: a systematic review and meta-analysis, Frontiers in Endocrinology, doi:10.3389/fendo.2024.1482853.frontiersin.org, doi.org.

Covid Analysis et al., May 2025, preprint, 1 author.

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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. IMA and WCH provide treatment protocols.

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