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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:
Hunt
MacFadden.
Submit updates/corrections.
Aug 12
Early, Late, PrEP, PEP Covid Analysis (Preprint) (meta analysis)
meta-analysis
Metformin for COVID-19: real-time meta analysis of 41 studies
Details   • Statistically significant improvements are seen for mortality, ventilation, and hospitalization. 24 studies from 23 independent teams in 8 different countries show statistically significant improvements in isolation (21 for the most ser..
Jul 8
Late Bramante et al. (Preprint) Results From the COVID-OUT Trial, a Phase-3 trial of Outpatient Treatment for Covid-19 Using Metformin, Ivermectin, and Fluvoxamine
Details   Results for COVID-OUT were reported in a presentation, however they are not currently available due to a news embargo. There were no statistically significant results for metformin, ivermectin, or fluvoxamine, except for a post-hoc metfor..
Jun 29
Early Hunt et al., Journal of General Internal Medicine, doi:10.1007/s11606-022-07701-3
death, ↓67.0%, p<0.0001
Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans
Details   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
PrEPPEP MacFadden et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156
cases, ↓1.0%, p=0.45
Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
Details   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
PrEPPEP Wong et al., Frontiers in Endocrinology, doi:10.3389/fendo.2022.810914
death, ↓59.0%, p=0.01
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
Details   Retrospective 1,214 COVID+ type 2 diabetes patients in Hong Kong, showing lower mortality and improved recovery with metformin use.
Feb 24
PrEPPEP Wong et al., Diabetes Care, doi:10.2337/dc21-2186
death, ↓51.0%, p<0.0001
Glycemic Control and Clinical Outcomes in U.S. Patients With COVID-19: Data From the National COVID Cohort Collaborative (N3C) Database
Details   N3C retrospective 39,616 COVID-19 patients with diabetes in the USA, showing lower mortality, ventilation, and hospitalization with metformin use.
Jan 18
PrEPPEP Usman et al., Journal of Thrombosis and Thrombolysis, doi:10.1007/s11239-022-02631-7
death, ↓59.8%, p=0.21
Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes
Details   Retrospective 75 diabetes patients, 34 on metformin, showing improved clinical outcomes with treatment, without statistical significance.
Jan 10
PrEPPEP Ojeda-Fernández et al., Diabetes, Obesity and Metabolism, doi:10.1111/dom.14648
death, ↓16.2%, p<0.0001
Metformin use is associated with a decrease in risk of hospitalization and mortality in COVID-19 diabetic patients: a population-based study in Lombardy
Details   Retrospective 31,966 COVID+ patients using anti-hyperglycemic drugs in Italy, showing lower mortality and ICU admission with metformin use.
Dec 31
2021
PrEPPEP Wallace et al., BMJ Open, doi:10.1136/bmjopen-2021-050051
death, ↓72.0%, p<0.0001
Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study
Details   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
PrEPPEP Al-Salameh et al., Diabetes & Metabolism, doi:10.1016/j.diabet.2021.101297
death/ICU, ↓55.5%, p=0.04
The association between metformin treatment and COVID-19 outcomes according to metformin continuation during hospitalisation
Details   Retrospective 140 diabetic patients in France, showing lower mortality for patients where metformin use was continued after hospitalization.
Nov 19
2021
In Vitro Parthasarathy et al., bioRxiv, doi:10.1101/2021.11.18.469078 (Preprint) (In Vitro)
In Vitro
Metformin Suppresses SARS-CoV-2 in Cell Culture
Details   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
PrEPPEP Bliden et al., Circulation, 144:A12228 (Preprint)
death, ↓59.8%, p=0.21
Metformin Use in Patients Hospitalized With COVID-19: Lower Inflammation, Oxidative Stress, and Thrombotic Risk Markers and Better Clinical Outcomes
Details   Retrospective 75 diabetes patients, 34 on metformin, showing lower mortality with treatment in unadjusted results with minimal group details.
Oct 30
2021
PrEPPEP Ong et al., Journal of the ASEAN Federation of Endocrine Societies, doi:10.15605/jafes.036.02.20
death, ↓46.8%, p=0.02
Association Between Metformin Use and Mortality Among Patients with Type 2 Diabetes Mellitus Hospitalized for COVID-19 Infection
Details   Retrospective 355 diabetic hospitalized COVID-19 patients in the Philippines, showing lower mortality with metformin use.
Oct 29
2021
PrEPPEP Saygili et al., Irish Journal of Medical Science, doi:10.1007/s11845-021-02823-9
death, ↓41.5%, p=0.02
Preadmission usage of metformin and mortality in COVID-19 patients including the post-discharge period
Details   Retrospective 586 diabetic hospitalized COVID-19 patients in Turkey, showing lower mortality with existing metformin use.
Oct 6
2021
PrEPPEP Wander et al., Diabetes Care, doi:10.2337/dc21-1351
death, ↓15.0%, p<0.0001
Prior Glucose-Lowering Medication Use and 30-Day Outcomes Among 64,892 Veterans With Diabetes and COVID-19
Details   Retrospective 64,892 veterans with diabetes in the USA, showing lower mortality with existing metformin use.
Sep 9
2021
PrEPPEP Ando et al., Scientific Reports, doi:10.1038/s41598-021-96720-x
hosp., ↓39.0%, p=0.04
Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States
Details   Retrospective 28,093 COVID+ patients in the USA, showing lower risk of hospitalization with metformin use.
Sep 7
2021
PrEPPEP Wang et al., BMJ Open Diabetes Research & Care, doi:10.1136/bmjdrc-2021-002299
ICU, ↓12.0%, p=0.005
Evaluation and management of COVID-19-related severity in people with type 2 diabetes
Details   Retrospective 16,504 COVID-19 type 2 diabetes patients, showing lower risk of ICU admission with existing metformin use.
Aug 31
2021
Meta Yang et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2021.108977 (meta analysis)
death, ↓36.0%, p<0.0001
The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus
Details   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
Early Reis et al., The Lancet Regional Health - Americas, doi:10.1016/j.lana.2021.100142 (preprint 8/31/21)
death, ↓26.6%, p=0.53
Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial
Details   RCT with 215 patients treated with metformin and 203 controls, showing no significant difference with treatment. For multiple major issues with this trial see . The hospitalization risk for off-protocol patients was several times higher i..
Aug 20
2021
PrEPPEP Cheng et al., Cell Metabolism, doi:10.1016/j.cmet.2020.08.013
death, ↑65.0%, p=0.25
Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes
Details   Retrospective 1,213 hospitalized diabetic COVID-19 patients in China, showing no significant difference in mortality with pre-existing metformin use.
Jul 18
2021
PrEPPEP Boye et al., Diabetes Therapy, doi:10.1007/s13300-021-01110-1
hosp., ↓10.0%, p<0.0001
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
Details   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
PrEPPEP Blanc et al., GeroScience, doi:10.1007/s11357-021-00397-z
death, ↓78.6%, p=0.06
Therapeutic prevention of COVID-19 in elderly: a case–control study
Details   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
Late Tamura et al., Diabetology & Metabolic Syndrome, doi:10.1186/s13098-021-00695-8
death, ↓96.6%, p=0.02
Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies
Details   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
PrEPPEP Ravindra et al., medRxiv, doi:10.1101/2021.04.20.21255792
death, ↓29.6%, p=0.42
Retrospective Assessment of Treatments of Hospitalized Covid-19 Patients
Details   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
PrEPPEP Alamgir et al., medRxiv, doi:10.1101/2021.03.22.21254110 (Preprint)
death, ↓27.0%, p<0.0001
Drug repositioning candidates identified using in-silico quasi-quantum molecular simulation demonstrate reduced COVID-19 mortality in 1.5M patient records
Details   In Silico study followed by PSM analysis of the National COVID Cohort Collaborative data in the USA, showing 27% lower mortality with metformin use. ABSTRACTBackgroundDru..
Mar 31
2021
PrEPPEP Ghany et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2021.02.022
death, ↓66.0%, p=0.0002
Metformin is associated with lower hospitalizations, mortality and severe coronavirus infection among elderly medicare minority patients in 8 states in USA
Details   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
PrEPPEP Jiang et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2020.108619
death, ↓46.0%, p=0.40
Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: A retrospective cohort study
Details   Retrospective 328 COVID-19 patients with type 2 diabetes in China, showing significantly lower risk of ARDS with existing metformin use.
Mar 30
2021
PrEPPEP Khunti et al., The Lacent Diabetes & Endocrinology, doi:10.1016/S2213-8587(21)00050-4
death, ↓23.0%, p<0.0001
Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England
Details   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
PrEPPEP Holt et al., Thorax, doi:10.1136/thoraxjnl-2021-217487
cases, ↑27.0%, p=0.42
Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
Details   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
PrEPPEP Wargny et al., Diabetologia, doi:10.1007/s00125-020-05351-w
death, ↓28.3%, p=0.03
Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study
Details   Retrospective 2,796 hospitalized diabetes patients with COVID-19 in France, showing lower mortality with metformin use.
Feb 13
2021
PrEPPEP Oh et al., Acta Diabetologica, doi:10.1007/s00592-020-01666-7
death, ↑26.0%, p=0.30
Metformin use and risk of COVID-19 among patients with type II diabetes mellitus: an NHIS-COVID-19 database cohort study
Details   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
PrEPPEP Lally et al., Journal of the American Medical Directors Association, doi:10.1016/j.jamda.2020.10.031
death, ↓52.0%, p=0.009
Metformin is Associated with Decreased 30-Day Mortality Among Nursing Home Residents Infected with SARS-CoV2
Details   Retrospective 775 nursing home residents in the USA, showing lower mortality with existing metformin use.
Jan 13
2021
PrEPPEP Crouse et al., Front. Endocrinol., doi:10.3389/fendo.2020.600439
death, ↓60.8%, p=0.02
Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes
Details   Retrospective 219 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment.
Dec 19
2020
PrEPPEP Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041
progression, ↑1.0%, p=0.11
Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
Details   Retrospective database analysis showing no significant differences with pre-existing metformin use.
Dec 10
2020
PrEPPEP Lalau et al., Diabetes & Metabolism, doi:10.1016/j.diabet.2020.101216
death, ↓22.2%, p=0.16
Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19
Details   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
PrEPPEP Bramante et al., The Lancet Healthy Longevity, doi:10.1016/S2666-7568(20)30033-7
death, ↓7.2%, p=0.15
Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis
Details   Retrospective 6,256 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment, statistically significant only for women.
Nov 16
2020
PrEPPEP Pérez-Belmonte et al., BMC Medicine, doi:10.1186/s12916-020-01832-2
death, ↑10.4%, p=0.48
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
Details   Retrospective 2,666 type 2 diabetes COVID-19 patients in Spain, showing higher mortality with existing metformin use (not statistically significant).
Nov 11
2020
Meta Lukito et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2020.11.006 (meta analysis)
meta-analysis
The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis
Details   Meta analysis of 9 studies showing lower mortality with metformin use.
Oct 19
2020
PrEPPEP Gao et al., Clinical and Translational Science, doi:10.1111/cts.12897
progression, ↑225.0%, p=0.045
Risk of Metformin in Patients With Type 2 Diabetes With COVID‐19: A Preliminary Retrospective Report
Details   Retrospective 110 hospitalized COVID-19 patients with diabetes in China, showing increased risk of severity with metformin.
Oct 13
2020
PrEPPEP Goodall et al., Epidemiology and Infection, doi:10.1017/S0950268820002472
death, ↓3.0%, p=0.81
Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study
Details   Retrospective 981 hospitalized patients in the UK, showing no significant difference with metformin use.
Oct 1
2020
PrEPPEP Li et al., Endocrine Practice, doi:10.4158/EP-2020-0466
death, ↓77.7%, p=0.02
Metformin Use in Diabetes Prior to Hospitalization: Effects on Mortality in Covid-19
Details   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
Meta Kow et al., Journal of Medical Virology, doi:10.1002/jmv.26498 (meta analysis)
meta-analysis
Mortality risk with preadmission metformin use in patients with COVID‐19 and diabetes: A meta‐analysis
Details   Meta analysis of 5 studies showing lower mortality with metformin use.
Aug 18
2020
Meta Hariyanto et al., Obesity Medicine, doi:10.1016/j.obmed.2020.100290 (meta analysis)
meta-analysis
Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection
Details   Meta analysis of 5 studies showing lower mortality with metformin use.
Aug 12
2020
PrEPPEP Kim et al., Diabetes & Metabolism Journal, doi:10.4093/dmj.2020.0146
death, ↓64.0%, p=0.10
The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea
Details   Retrospective 235 hospitalized diabetes patients in South Korea, showing lower mortality and lower progression to severe disease with metformin.
Jul 31
2020
PrEPPEP Chen et al., Diabetes Care, doi:10.2337/dc20-0660
death, ↓33.0%, p=0.46
Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication
Details   Retrospective 120 COVID-19 diabetes patients, showing non-statistically significantly lower mortality with existing metformin treatment.
Jul 14
2020
PrEPPEP Wang et al., Journal of Hematology & Oncology, doi:10.1186/s13045-020-00934-x
death, ↓57.7%, p=0.43
A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward
Details   Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing non-statistically significant lower mortality with metformin treatment.
Jun 23
2020
PrEPPEP Choi et al., Journal of Clinical Medicine, doi:10.3390/jcm9061959
progression, ↑100%, p=0.26
Clinical Characteristics and Disease Progression in Early-Stage COVID-19 Patients in South Korea
Details   Retrospective 293 patients in South Korea, showing higher risk of progression with metformin use, without statistical significance.
May 21
2020
PrEPPEP Luo et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-0375
death, ↓74.7%, p=0.02
Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis
Details   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 both valuable and complementary. All practical, effective, and safe means should be used. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases mortality, morbidity, collateral damage, and the risk of endemic status. 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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