Metformin for COVID-19: real-time analysis of all 12 studies

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Database of all 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. Submit updates/corrections.

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Nov 19	In Vitro	Tandel 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 19	Details Source PDF In Vitro In Vitro
	Tandel 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. Tandel et al., 11/19/2021, preprint, 3 authors. In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Oct 6	PrEPPEP	Wander et al., Diabetes Care, doi:10.2337/dc21-1351 (Peer Reviewed)	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.
Oct 6	Details Source PDF Prophylaxis study Prophylaxis study
	Wander et al., Diabetes Care, doi:10.2337/dc21-1351 (Peer Reviewed)
	Prior Glucose-Lowering Medication Use and 30-Day Outcomes Among 64,892 Veterans With Diabetes and COVID-19
	Retrospective 64,892 veterans with diabetes in the USA, showing lower mortality with existing metformin use. risk of death, 15.0% lower, RR 0.85, p < 0.001, treatment 29,685, control 35,207, OR converted to RR, logistic regression, within 30 days of diagnosis, control prevalance approximated with overall prevalence. risk of ICU admission, 1.9% lower, RR 0.98, p = 0.62, treatment 29,685, control 35,207, OR converted to RR, logistic regression, within 30 days of diagnosis, control prevalance approximated with overall prevalence. risk of hospitalization, 3.2% lower, RR 0.97, p = 0.09, treatment 29,685, control 35,207, OR converted to RR, logistic regression, within 30 days of diagnosis, control prevalance approximated with overall prevalence. Wander et al., 10/6/2021, retrospective, database analysis, USA, North America, peer-reviewed, 8 authors.
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Aug 31	Early	Reis et al., Preprint (Preprint)	hosp./ER, ↑15.0%, p=0.56	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 217 patients treated with metformin and 206 controls, showing no significant difference with treatment. Limited information is provided in the preprint. Time since symptom onset is not specified. The trial may share some similar ..
Aug 31	Details Source PDF Early treatment study Early treatment study
	Reis et al., Preprint (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
	RCT with 217 patients treated with metformin and 206 controls, showing no significant difference with treatment. Limited information is provided in the preprint. Time since symptom onset is not specified. The trial may share some similar issues with the companion ivermectin trial [1]. [1] c19ivermectin.com/togetherivm.html extended ER observation or hospitalization, 15.0% higher, RR 1.15, p = 0.56, treatment 32 of 217 (14.7%), control 27 of 206 (13.1%), ITT. extended ER observation or hospitalization, 18.0% higher, RR 1.18, p = 0.50, treatment 217, control 206, per protocol. risk of no virological cure, 3.8% lower, RR 0.96, p = 0.57, treatment 217, control 206, adjusted. Reis et al., 8/31/2021, Double Blind Randomized Controlled Trial, Brazil, South America, preprint, 13 authors.
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May 5	PrEPPEP	Ravindra et al., medRxiv, doi:10.1101/2021.04.20.21255792 (Peer Reviewed)	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.
May 5	Details Source PDF Prophylaxis study Prophylaxis study
	Ravindra et al., medRxiv, doi:10.1101/2021.04.20.21255792 (Peer Reviewed)
	Retrospective Assessment of Treatments of Hospitalized Covid-19 Patients
	Retrospective 1,035 hospitalized patients in India. Of 366 diabetic patients, there was lower mortality for the 53 that were on metformin. risk of death, 29.6% lower, RR 0.70, p = 0.42, treatment 5 of 53 (9.4%), control 57 of 313 (18.2%), adjusted, OR converted to RR. Excluded in after exclusion results of meta analysis: minimal details provided. Ravindra et al., 5/5/2021, retrospective, India, South Asia, peer-reviewed, 14 authors.
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Mar 30	PrEPPEP	Khunti et al., The Lacent Diabetes & Endocrinology, doi:10.1016/S2213-8587(21)00050-4 (Peer Reviewed)	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	Details Source PDF Prophylaxis study Prophylaxis study
	Khunti et al., The Lacent Diabetes & Endocrinology, doi:10.1016/S2213-8587(21)00050-4 (Peer Reviewed)
	Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England
	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 diabetes. risk of death, 23.0% lower, RR 0.77, p < 0.001, adjusted. Khunti et al., 3/30/2021, retrospective, population-based cohort, United Kingdom, Europe, peer-reviewed, 15 authors.
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Mar 30	PrEPPEP	Holt et al., medRxiv, doi:10.1101/2021.03.27.21254452 (Preprint)	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..
Mar 30	Details Source PDF Prophylaxis study Prophylaxis study
	Holt et al., medRxiv, doi:10.1101/2021.03.27.21254452 (Preprint)
	Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
	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. Statistical significance was not reached for any of these. Results are subject to confounding, with only the vitamin D result fully adjusted. NCT04330599. COVIDENCE UK. risk of case, 27.0% higher, RR 1.27, p = 0.42, treatment 12 of 429 (2.8%), control 434 of 14,798 (2.9%), adjusted, OR converted to RR, minimally adjusted, group sizes approximated. Excluded in after exclusion results of meta analysis: significant unadjusted confounding possible. Holt et al., 3/30/2021, prospective, United Kingdom, Europe, preprint, 31 authors.
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Jan 13	PrEPPEP	Crouse et al., Front. Endocrinol., doi:10.3389/fendo.2020.600439 (Peer Reviewed)	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.
Jan 13	Details Source PDF Prophylaxis study Prophylaxis study
	Crouse et al., Front. Endocrinol., doi:10.3389/fendo.2020.600439 (Peer Reviewed)
	Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes
	Retrospective 219 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment. risk of death, 60.8% lower, RR 0.39, p = 0.02, treatment 8 of 76 (10.5%), control 34 of 144 (23.6%), adjusted, OR converted to RR, multiple logistic regression. Crouse et al., 1/13/2021, retrospective, USA, North America, peer-reviewed, 6 authors.
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Dec 19 2020	PrEPPEP	Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 (Peer Reviewed)	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 with 17 existing users of HCQ and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and authors..
Dec 19 2020	Details Source PDF Prophylaxis study Prophylaxis study
	Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041 (Peer Reviewed)
	Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
	Retrospective database analysis with 17 existing users of HCQ and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [1]. [1] c19hcq.com/ferri.html risk of disease progression, 1.0% higher, RR 1.01, p = 0.11, treatment 104 of 272 (38.2%), control 774 of 2,533 (30.6%), adjusted, multivariate. risk of case, 4.0% lower, RR 0.96, p = 0.82, treatment 329 of 1,874 (17.6%), control 7,012 of 42,172 (16.6%), adjusted, multivariate. Huh et al., 12/19/2020, retrospective, database analysis, South Korea, Asia, peer-reviewed, 8 authors.
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Dec 3 2020	PrEPPEP	Bramante et al., The Lancet Healthy Longevity, doi:10.1016/S2666-7568(20)30033-7 (Peer Reviewed)	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.
Dec 3 2020	Details Source PDF Prophylaxis study Prophylaxis study
	Bramante et al., The Lancet Healthy Longevity, doi:10.1016/S2666-7568(20)30033-7 (Peer Reviewed)
	Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis
	Retrospective 6,256 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment, statistically significant only for women. risk of death, 7.2% lower, RR 0.93, p = 0.15, treatment 394 of 2,333 (16.9%), control 791 of 3,923 (20.2%), OR converted to RR, PSM, all patients. risk of death, 24.1% lower, RR 0.76, p = 0.02, treatment 1,129, control 2,173, PSM, women, RR approximated with OR. risk of death, 3.5% higher, RR 1.03, p = 0.75, treatment 1,204, control 1,750, PSM, men, RR approximated with OR. Bramante et al., 12/3/2020, retrospective, database analysis, USA, North America, peer-reviewed, 17 authors.
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Jul 31 2020	PrEPPEP	Chen et al., Diabetes Care, doi:10.2337/dc20-0660 (Peer Reviewed)	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 31 2020	Details Source PDF Prophylaxis study Prophylaxis study
	Chen et al., Diabetes Care, doi:10.2337/dc20-0660 (Peer Reviewed)
	Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication
	Retrospective 120 COVID-19 diabetes patients, showing non-statistically significantly lower mortality with existing metformin treatment. risk of death, 33.0% lower, RR 0.67, p = 0.46, treatment 4 of 43 (9.3%), control 15 of 77 (19.5%), adjusted, OR converted to RR. Chen et al., 7/31/2020, retrospective, China, Asia, peer-reviewed, 12 authors.
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Jul 14 2020	PrEPPEP	Wang et al., Journal of Hematology & Oncology, doi:10.1186/s13045-020-00934-x (Peer Reviewed)	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.
Jul 14 2020	Details Source PDF Prophylaxis study Prophylaxis study
	Wang et al., Journal of Hematology & Oncology, doi:10.1186/s13045-020-00934-x (Peer Reviewed)
	A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward
	Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing non-statistically significant lower mortality with metformin treatment. risk of death, 57.7% lower, RR 0.42, p = 0.43, treatment 1 of 9 (11.1%), control 13 of 49 (26.5%), OR converted to RR. Wang et al., 7/14/2020, retrospective, USA, North America, peer-reviewed, 13 authors.
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May 21 2020	PrEPPEP	Luo et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-0375 (Peer Reviewed)	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.
May 21 2020	Details Source PDF Prophylaxis study Prophylaxis study
	Luo et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-0375 (Peer Reviewed)
	Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis
	Retrospective 283 COVID-19+ diabetes patients in China, showing lower mortality with existing metformin treatment. risk of death, 74.7% lower, RR 0.25, p = 0.02, treatment 3 of 104 (2.9%), control 22 of 179 (12.3%), adjusted, OR converted to RR, multivariate. Luo et al., 5/21/2020, retrospective, China, Asia, peer-reviewed, 9 authors.
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Please send us corrections, updates, or comments. Vaccines and treatments are both extremely valuable and complementary. All practical, effective, and safe means should be used. Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage. 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. Treatment protocols for physicians are available from the FLCCC.

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