Metformin for COVID-19
Lower risk for mortality, ventilation, ICU, hospitalization, progression, recovery, and viral clearance.
No treatment is 100% effective.
Protocols combine treatments.
Meta analysis of 22 metformin studies, showing significantly lower mortality with metformin use prior to hospitalization.
24 meta-analyses show significant improvements with metformin for mortality1-23,
hospitalization7,13,23 ,
progression1, and
severity8,9,13 .
Currently there are 114 metformin for COVID-19 studies, showing 36% lower mortality [32‑40%], 30% lower ventilation [13‑43%], 19% lower ICU admission [8‑28%], 18% lower hospitalization [12‑23%], and 5% fewer cases [-3‑12%].
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
20.
Scheen, A., Metformin and COVID-19: From cellular mechanisms to reduced mortality, Diabetes & Metabolism, doi:10.1016/j.diabet.2020.07.006.
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.
Ma et al., 23 Feb 2023, peer-reviewed, 2 authors.
Contact: mahesh.krishnamurthy@sluhn.org.
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
Background Coronavirus disease 2019 (COVID-19) is a new pandemic that the entire world is facing since December of 2019. Increasing evidence has shown that metformin is linked to favorable outcomes in patients with COVID-19. The aim of this study was to address whether outpatient or inpatient metformin therapy for type 2 diabetes mellitus is associated with low inhospital mortality in patients hospitalized for COVID-19.
Methods We searched studies published in PubMed, Embase, Google Scholar and Cochrane Library up to November 1, 2022. Raw event data extracted from individual study were pooled using the Mantel-Haenszel approach. Odds ratio (OR) or hazard ratio (HR) adjusted for covariates that potentially confound the association using multivariable regression or propensity score matching was pooled by the inverse-variance method. Random effect models were applied for meta-analysis due to variance among studies.
Results Twenty-two retrospective observational studies were selected. The pooled unadjusted OR for outpatient metformin therapy and in-hospital mortality was 0.48 (95% CI, 0.37-0.62) and the pooled OR adjusted with multivariable regression or propensity score matching was 0.71 (95% CI, 0.50-0.99). The pooled unadjusted OR for inpatient metformin therapy and in-hospital mortality was 0.18 (95% CI, 0.10-0.31), whereas the pooled adjusted HR was 1.10 (95% CI, 0.38-3.15).
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DOI record:
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"abstract": "<jats:sec id=\"sec001\">\n<jats:title>Background</jats:title>\n<jats:p>Coronavirus disease 2019 (COVID-19) is a new pandemic that the entire world is facing since December of 2019. Increasing evidence has shown that metformin is linked to favorable outcomes in patients with COVID-19. The aim of this study was to address whether outpatient or inpatient metformin therapy for type 2 diabetes mellitus is associated with low in-hospital mortality in patients hospitalized for COVID-19.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods</jats:title>\n<jats:p>We searched studies published in PubMed, Embase, Google Scholar and Cochrane Library up to November 1, 2022. Raw event data extracted from individual study were pooled using the Mantel-Haenszel approach. Odds ratio (OR) or hazard ratio (HR) adjusted for covariates that potentially confound the association using multivariable regression or propensity score matching was pooled by the inverse-variance method. Random effect models were applied for meta-analysis due to variance among studies.</jats:p>\n</jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results</jats:title>\n<jats:p>Twenty-two retrospective observational studies were selected. The pooled unadjusted OR for outpatient metformin therapy and in-hospital mortality was 0.48 (95% CI, 0.37–0.62) and the pooled OR adjusted with multivariable regression or propensity score matching was 0.71 (95% CI, 0.50–0.99). The pooled unadjusted OR for inpatient metformin therapy and in-hospital mortality was 0.18 (95% CI, 0.10–0.31), whereas the pooled adjusted HR was 1.10 (95% CI, 0.38–3.15).</jats:p>\n</jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusions</jats:title>\n<jats:p>Our results suggest that there is a significant association between the reduction of in-hospital mortality and outpatient metformin therapy for type 2 diabetes mellitus in patients hospitalized for COVID-19.</jats:p>\n</jats:sec>",
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