Metformin COVID-19 studies. Most studies analyze existing use with diabetic patients. Many
results are subject to confounding by indication — metformin is
typically used early in the progression of type 2 diabetes. Prophylaxis
results typically include continuing use after infection and
hospitalization, and greater benefit is seen for more serious outcomes.
The beneficial effect of metformin may be more related to later stages of
COVID-19.
Recent:Yip Cousins Kolin Chan Shestakova Loucera Hunt.
Submit updates/corrections .
Sep 30 |
(Preprint) (meta analysis) | Metformin for COVID-19: real-time meta analysis of 48 studies |
| Statistically significant improvements are seen for mortality, ventilation, ICU admission, and hospitalization. 28 studies from 27 independent teams in 10 different countries show statistically significant improvements in isolation (24 .. | ||
Sep 21 |
et al., SSRN Electronic Journal, doi:10.2139/ssrn.4225660 | Metformin Does Not Reduce Hospitalisation for COVID-19 |
| 7% lower combined mortality/hospitalization [p=0.61] and 15% lower progression [p=0.16]. Retrospective 12,331 diabetes patients in Hong Kong, showing no significant difference in outcomes with metformin use. | ||
Aug 30 |
et al., medRxiv, doi:10.1101/2022.08.29.22279355 (Preprint) | Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes |
| 59% lower mortality [p=0.66], 54% lower severe cases [p=0.37], and 42% lower progression [p=0.37]. Retrospective 3,136 patients with prediabetes and 282 with PCOS, showing metformin associated with reduced COVID-19 severity. | ||
Aug 18 |
et al., NEJM, doi:10.1056/NEJMoa2201662 | Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19 |
| 52% lower combined mortality/hospitalization [p=0.09] and 40% lower progression [p=0.03]. COVID-OUT remotely operated RCT, showing lower combined ER/hospitalization/death with metformin. Results for other treatments are listed separately - ivermectin , fluvoxamine . The "control" group includes patients receiving active treatm.. | ||
Aug 16 |
et al., medRxiv, doi:10.1101/2022.08.14.22278751 (Preprint) | Real-world evidence with a retrospective cohort of 15,968 Andalusian COVID-19 hospitalized patients suggests 21 new effective treatments and one drug that increases death risk |
| 30% lower mortality [p<0.0001]. Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, aspirin, vitamin D, vitamin C, and budesonide. | ||
Aug 9 |
et al., Frontiers in Endocrinology, doi:10.3389/fendo.2022.909874 | Risk factors for COVID-19 case fatality rate in people with type 1 and type 2 diabetes mellitus: A nationwide retrospective cohort study of 235,248 patients in the Russian Federation |
| 22% lower mortality [p=0.001]. Retrospective 224,190 type 2 diabetes patients in Russia, showing lower mortality with metformin use. | ||
Jul 6 |
et al., medRxiv, doi:10.1101/2022.07.02.22277181 (Preprint) | Integrative analysis of viral entry networks and clinical outcomes identifies a protective role for spironolactone in severe COVID-19 |
| 54% lower ventilation [p=0.007] and 56% lower ICU admission [p<0.0001]. PSM retrospective 64,349 COVID-19 patients in the USA, showing metformin associated with lower ICU admission and mechanical ventilation. | ||
Jun 29 |
et al., Journal of General Internal Medicine, doi:10.1007/s11606-022-07701-3 | Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans |
| 67% lower mortality [p<0.0001]. Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including metformin. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a cont.. | ||
Mar 29 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156 | Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications |
| 1% fewer cases [p=0.45]. Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant differences in cases with chronic use of metformin. | ||
Mar 7 |
et al., Frontiers in Endocrinology, doi:10.3389/fendo.2022.810914 | Metformin Use in Relation to Clinical Outcomes and Hyperinflammatory Syndrome Among COVID-19 Patients With Type 2 Diabetes: A Propensity Score Analysis of a Territory-Wide Cohort |
| 59% lower mortality [p=0.01], 61% improved recovery [p=0.005], 64% better improvement [p=0.009], and 56% higher hospital discharge [p=0.009]. Retrospective 1,214 COVID+ type 2 diabetes patients in Hong Kong, showing lower mortality and improved recovery with metformin use. | ||
Feb 24 |
et al., Diabetes Care, doi:10.2337/dc21-2186 | Glycemic Control and Clinical Outcomes in U.S. Patients With COVID-19: Data From the National COVID Cohort Collaborative (N3C) Database |
| 51% lower mortality [p<0.0001], 41% lower ventilation [p<0.0001], and 40% lower hospitalization [p<0.0001]. N3C retrospective 39,616 COVID-19 patients with diabetes in the USA, showing lower mortality, ventilation, and hospitalization with metformin use. | ||
Jan 18 |
et al., Journal of Thrombosis and Thrombolysis, doi:10.1007/s11239-022-02631-7 | Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes |
| 60% lower mortality [p=0.21], 76% lower ventilation [p=0.05], and 34% shorter hospitalization [p=0.13]. Retrospective 75 diabetes patients, 34 on metformin, showing improved clinical outcomes with treatment, without statistical significance. | ||
Jan 10 |
et al., Diabetes, Obesity and Metabolism, doi:10.1111/dom.14648 | Metformin use is associated with a decrease in risk of hospitalization and mortality in COVID-19 diabetic patients: a population-based study in Lombardy |
| 16% lower mortality [p<0.0001], 22% lower ICU admission [p=0.01], and 3% lower hospitalization [p=0.11]. Retrospective 31,966 COVID+ patients using anti-hyperglycemic drugs in Italy, showing lower mortality and ICU admission with metformin use. | ||
Dec 31 2021 |
et al., BMJ Open, doi:10.1136/bmjopen-2021-050051 | Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study |
| 72% lower mortality [p<0.0001]. Retrospective 9,532 hospitalized COVID+ veterans in the USA, showing lower mortality with metformin use. The study provides results for use before, after, and before+after. Before+after should more accurately represent prophylaxis up to C.. | ||
Nov 30 2021 |
et al., Diabetes & Metabolism, doi:10.1016/j.diabet.2021.101297 | The association between metformin treatment and COVID-19 outcomes according to metformin continuation during hospitalisation |
| 55% lower combined mortality/ICU admission [p=0.04]. Retrospective 140 diabetic patients in France, showing lower mortality for patients where metformin use was continued after hospitalization. | ||
Nov 19 2021 |
et al., bioRxiv, doi:10.1101/2021.11.18.469078 (Preprint) (In Vitro) | Metformin Suppresses SARS-CoV-2 in Cell Culture |
| In Vitro study showing metformin inhibits SARS-CoV-2 in Caco2 cells. Metformin reduced viral titers by nearly 99%, and by about 90% when cells were treated prior to infection. | ||
Nov 8 2021 |
et al., Circulation, 144:A12228 (Preprint) | Metformin Use in Patients Hospitalized With COVID-19: Lower Inflammation, Oxidative Stress, and Thrombotic Risk Markers and Better Clinical Outcomes |
| 60% lower mortality [p=0.21] and 76% lower ventilation [p=0.05]. Retrospective 75 diabetes patients, 34 on metformin, showing lower mortality with treatment in unadjusted results with minimal group details. | ||
Oct 30 2021 |
et al., Journal of the ASEAN Federation of Endocrine Societies, doi:10.15605/jafes.036.02.20 | Association Between Metformin Use and Mortality Among Patients with Type 2 Diabetes Mellitus Hospitalized for COVID-19 Infection |
| 47% lower mortality [p=0.02]. Retrospective 355 diabetic hospitalized COVID-19 patients in the Philippines, showing lower mortality with metformin use. | ||
Oct 29 2021 |
et al., Irish Journal of Medical Science, doi:10.1007/s11845-021-02823-9 | Preadmission usage of metformin and mortality in COVID-19 patients including the post-discharge period |
| 42% lower mortality [p=0.02]. Retrospective 586 diabetic hospitalized COVID-19 patients in Turkey, showing lower mortality with existing metformin use. | ||
Oct 6 2021 |
et al., Diabetes Care, doi:10.2337/dc21-1351 | Prior Glucose-Lowering Medication Use and 30-Day Outcomes Among 64,892 Veterans With Diabetes and COVID-19 |
| 15% lower mortality [p<0.0001], 2% lower ICU admission [p=0.62], and 3% lower hospitalization [p=0.09]. Retrospective 64,892 veterans with diabetes in the USA, showing lower mortality with existing metformin use. | ||
Sep 9 2021 |
et al., Scientific Reports, doi:10.1038/s41598-021-96720-x | Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States |
| 39% lower hospitalization [p=0.04]. Retrospective 28,093 COVID+ patients in the USA, showing lower risk of hospitalization with metformin use. | ||
Sep 7 2021 |
et al., BMJ Open Diabetes Research & Care, doi:10.1136/bmjdrc-2021-002299 | Evaluation and management of COVID-19-related severity in people with type 2 diabetes |
| 12% lower ICU admission [p=0.005]. Retrospective 16,504 COVID-19 type 2 diabetes patients, showing lower risk of ICU admission with existing metformin use. | ||
Aug 31 2021 |
et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2021.108977 (meta analysis) | The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus |
| 36% lower mortality [p<0.0001]. Meta analysis of 17 studies including 20,719 COVID-19 patients with diabetes, showing lower risk of mortality and severity with metformin. | ||
Aug 31 2021 |
et al., The Lancet Regional Health - Americas, doi:10.1016/j.lana.2021.100142 (date from earlier preprint) | Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial |
| 27% lower mortality [p=0.53], 6% lower hospitalization [p=0.88], 14% more combined hospitalization/ER visits [p=0.58], and 31% lower progression [p=0.48]. Data for the primary outcome in this trial appears to be impossible . For example, considering the metformin arm and the ITT population: 24 were hospitalized and 8 had an ER visit (tables S2/S3), therefore the number for combined ER or.. | ||
Aug 20 2021 |
et al., Cell Metabolism, doi:10.1016/j.cmet.2020.08.013 | Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes |
| 65% higher mortality [p=0.25]. Retrospective 1,213 hospitalized diabetic COVID-19 patients in China, showing no significant difference in mortality with pre-existing metformin use. | ||
Jul 18 2021 |
et al., Diabetes Therapy, doi:10.1007/s13300-021-01110-1 | Risk Factors Associated with COVID-19 Hospitalization and Mortality: A Large Claims-Based Analysis Among People with Type 2 Diabetes Mellitus in the United States |
| 10% lower hospitalization [p<0.0001]. Retrospective 9531 COVID+ diabetes patients in the USA, showing lower risk of hospitalization with existing biguanides treatment (defined as mainly metformin in the abstract and entirely metformin in the text). | ||
Jul 17 2021 |
et al., GeroScience, doi:10.1007/s11357-021-00397-z | Therapeutic prevention of COVID-19 in elderly: a case–control study |
| 79% lower mortality [p=0.06] and 44% more cases [p=0.12]. Retrospective 179 patients in France exposed to COVID-19 showing, without statistical significance, a higher risk of cases, and a lower risk of mortality among cases with existing metformin treatment. | ||
Jul 13 2021 |
et al., Diabetology & Metabolic Syndrome, doi:10.1186/s13098-021-00695-8 | Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies |
| 97% lower mortality [p=0.02]. Retrospective 188 hospitalized patients in Brazil, showing lower risk of mortality with metformin use. Authors note that, although pre-hospital metformin use improved clinical parameters at admission, continuous use during hospitalization.. | ||
May 5 2021 |
et al., medRxiv, doi:10.1101/2021.04.20.21255792 | Retrospective Assessment of Treatments of Hospitalized Covid-19 Patients |
| 30% lower mortality [p=0.42]. Retrospective 1,035 hospitalized patients in India. Of 366 diabetic patients, there was lower mortality for the 53 that were on metformin. | ||
Apr 6 2021 |
et al., medRxiv, doi:10.1101/2021.03.22.21254110 (Preprint) | Drug repositioning candidates identified using in-silico quasi-quantum molecular simulation demonstrate reduced COVID-19 mortality in 1.5M patient records |
|
27% lower mortality [p<0.0001].
In Silico study followed by PSM analysis of the National COVID Cohort Collaborative data in the USA, showing 27% lower mortality with metformin use. |
||
Mar 31 2021 |
et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2021.02.022 | Metformin is associated with lower hospitalizations, mortality and severe coronavirus infection among elderly medicare minority patients in 8 states in USA |
| 66% lower mortality [p=0.0002], 29% lower hospitalization [p=0.008], and 68% lower ARDS [p<0.0001]. Retrospective 1,139 elderly COVID+ patients in the USA, 392 with pre-existing metformin use, showing significantly lower mortality, hospitalization, and ARDS with treatment. | ||
Mar 31 2021 |
et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2020.108619 | Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: A retrospective cohort study |
| 46% lower mortality [p=0.4] and 80% lower progression [p=0.02]. Retrospective 328 COVID-19 patients with type 2 diabetes in China, showing significantly lower risk of ARDS with existing metformin use. | ||
Mar 30 2021 |
et al., The Lacent Diabetes & Endocrinology, doi:10.1016/S2213-8587(21)00050-4 | Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England |
| 23% lower mortality [p<0.0001]. Retrospective 2,851,465 people with type 2 diabetes in the UK, showing lower mortality with existing metformin use. Results are subject to confounding by indication because metformin is typically used early in the progression of type 2 di.. | ||
Mar 30 2021 |
et al., Thorax, doi:10.1136/thoraxjnl-2021-217487 | Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK) |
| 27% more cases [p=0.42]. Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistica.. | ||
Feb 17 2021 |
et al., Diabetologia, doi:10.1007/s00125-020-05351-w | Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study |
| 28% lower mortality [p=0.03] and 15% higher hospital discharge [p=0.02]. Retrospective 2,796 hospitalized diabetes patients with COVID-19 in France, showing lower mortality with metformin use. | ||
Feb 13 2021 |
et al., Acta Diabetologica, doi:10.1007/s00592-020-01666-7 | Metformin use and risk of COVID-19 among patients with type II diabetes mellitus: an NHIS-COVID-19 database cohort study |
| 26% higher mortality [p=0.3] and 28% fewer cases [p<0.0001]. Retrospective 27,493 type II diabetes patients in the USA, 7,204 on metformin, showing significantly lower COVID-19 cases, but no significant difference in mortality. | ||
Jan 31 2021 |
et al., Journal of the American Medical Directors Association, doi:10.1016/j.jamda.2020.10.031 | Metformin is Associated with Decreased 30-Day Mortality Among Nursing Home Residents Infected with SARS-CoV2 |
| 52% lower mortality [p=0.009]. Retrospective 775 nursing home residents in the USA, showing lower mortality with existing metformin use. | ||
Jan 13 2021 |
et al., Front. Endocrinol., doi:10.3389/fendo.2020.600439 | Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes |
| 61% lower mortality [p=0.02]. Retrospective 219 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment. | ||
Dec 19 2020 |
et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 | Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea |
| 1% higher progression [p=0.11] and 4% fewer cases [p=0.82]. Retrospective database analysis showing no significant differences with pre-existing metformin use. | ||
Dec 10 2020 |
et al., Diabetes & Metabolism, doi:10.1016/j.diabet.2020.101216 | Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19 |
| 22% lower mortality [p=0.16], 18% lower combined mortality/intubation [p=0.21], and 7% lower ventilation [p=0.72]. Retrospective 2,449 hospitalized COVID-19 diabetes patients in France, 1,496 with existing metformin use, showing lower mortality with treatment. Statistical significance was reached in model 1 but not in models 2-4 which also adjust for .. | ||
Dec 3 2020 |
et al., The Lancet Healthy Longevity, doi:10.1016/S2666-7568(20)30033-7 | Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis |
| 7% lower mortality [p=0.15]. Retrospective 6,256 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment, statistically significant only for women. | ||
Nov 17 2020 |
et al., PLOS ONE, doi:10.1371/journal.pone.0241264 | Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank |
| 30% more cases [p=0.08]. 397,064 patient UK Biobank retrospective showing higher risk of COVID-19 with metformin use, without statistical significance. | ||
Nov 16 2020 |
et al., BMC Medicine, doi:10.1186/s12916-020-01832-2 | Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study |
| 10% higher mortality [p=0.48]. Retrospective 2,666 type 2 diabetes COVID-19 patients in Spain, showing higher mortality with existing metformin use (not statistically significant). | ||
Nov 11 2020 |
et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2020.11.006 (meta analysis) | The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis |
| Meta analysis of 9 studies showing lower mortality with metformin use. | ||
Oct 19 2020 |
et al., Clinical and Translational Science, doi:10.1111/cts.12897 | Risk of Metformin in Patients With Type 2 Diabetes With COVID‐19: A Preliminary Retrospective Report |
| 225% higher progression [p=0.05]. Retrospective 110 hospitalized COVID-19 patients with diabetes in China, showing increased risk of severity with metformin. | ||
Oct 13 2020 |
et al., Epidemiology and Infection, doi:10.1017/S0950268820002472 | Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study |
| 3% lower mortality [p=0.81]. Retrospective 981 hospitalized patients in the UK, showing no significant difference with metformin use. | ||
Oct 1 2020 |
et al., Endocrine Practice, doi:10.4158/EP-2020-0466 | Metformin Use in Diabetes Prior to Hospitalization: Effects on Mortality in Covid-19 |
| 78% lower mortality [p=0.02]. Retrospective 131 type II diabetes patients with COVID pneumonia, showing lower mortality with existing metformin use. Acarbose (commonly used in China as an initial therapy for diabetes) did not have a similar association with mortality,.. | ||
Sep 30 2020 |
et al., Journal of Medical Virology, doi:10.1002/jmv.26498 (meta analysis) | Mortality risk with preadmission metformin use in patients with COVID‐19 and diabetes: A meta‐analysis |
| Meta analysis of 5 studies showing lower mortality with metformin use. | ||
Aug 18 2020 |
et al., Obesity Medicine, doi:10.1016/j.obmed.2020.100290 (meta analysis) | Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection |
| Meta analysis of 5 studies showing lower mortality with metformin use. | ||
Aug 12 2020 |
et al., Diabetes & Metabolism Journal, doi:10.4093/dmj.2020.0146 | The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea |
| 64% lower mortality [p=0.1] and 52% lower progression [p=0.13]. Retrospective 235 hospitalized diabetes patients in South Korea, showing lower mortality and lower progression to severe disease with metformin. | ||
Jul 31 2020 |
et al., Diabetes Care, doi:10.2337/dc20-0660 | Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication |
| 33% lower mortality [p=0.46]. Retrospective 120 COVID-19 diabetes patients, showing non-statistically significantly lower mortality with existing metformin treatment. | ||
Jul 14 2020 |
et al., Journal of Hematology & Oncology, doi:10.1186/s13045-020-00934-x | A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward |
| 58% lower mortality [p=0.43]. Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing non-statistically significant lower mortality with metformin treatment. | ||
Jun 23 2020 |
et al., Journal of Clinical Medicine, doi:10.3390/jcm9061959 | Clinical Characteristics and Disease Progression in Early-Stage COVID-19 Patients in South Korea |
| 120% higher progression [p=0.26]. Retrospective 293 patients in South Korea, showing higher risk of progression with metformin use, without statistical significance. | ||
May 21 2020 |
et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-0375 | Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis |
| 75% lower mortality [p=0.02]. Retrospective 283 COVID-19+ diabetes patients in China, showing lower mortality with existing metformin treatment. | ||
Please send us corrections, updates, or comments. 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.
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that studies are listed under the date they were first available, which may be
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