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Summary of COVID-19 metformin studies

Studies   Meta Analysis   Hide extended summaries

20 patient metformin late treatment RCT: 44% lower need for oxygen therapy (p=0.03), 10% shorter hospitalization (p=0.35), and 41% faster viral clearance (p=0.03).
RCT 20 hospitalized COVID-19 patients showing faster viral load reduction and lower oxygen use with metformin glycinate 620mg twice daily for 14 days compared to placebo. The in vitro portion demonstrated inhibition of viral replication and cytopathic effects with metformin glycinate pretreatment.

Aug 2022, Biomedicine & Pharmacotherapy, https://www.sciencedirect.com/science/article/pii/S0753332222006126, https://c19p.org/venturalopez

1,214 patient metformin prophylaxis study: 59% lower mortality (p=0.01), 61% improved recovery (p=0.005), 64% greater 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.

Mar 2022, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2022.810914/full, https://c19p.org/wong

1,139 patient metformin prophylaxis study: 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 2021, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://www.sciencedirect.com/science/article/pii/S187140212100045X, https://c19p.org/ghany

556 patient metformin prophylaxis study: 60% lower mortality (p=0.02), 72% lower ventilation (p=0.008), 39% lower ICU admission (p=0.12), and 30% lower need for oxygen therapy (p=0.23).
Retrospective 556 diabetic patients in South Korea with COVID-19 showing lower risk of mechanical ventilation and death with metformin, lower risks of oxygen treatment and death with DPP-4 inhibitors, and increased risk of mechanical ventilation with sulfonylureas. The study used nationwide data to analyze the impact of common antidiabetic medications on COVID-19 outcomes. Authors note that South Korea had a policy early in the pandemic of hospitalizing nearly all confirmed COVID-19 patients regardless of severity.

Jan 2024, Endocrinology and Metabolism, http://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2024.1857, https://c19p.org/jang6

4,922 patient metformin prophylaxis PSM study: 52% lower mortality (p=0.01), 54% lower ventilation (p=0.007), and 72% lower ARDS (p=0.04).
Retrospective 4,922 COVID-19 patients with type 2 diabetes in China, showing lower mortality with metformin and alpha-glucosidase inhibitor treatment and higher mortality with insulin treatment.

May 2024, Molecular Biomedicine, https://link.springer.com/10.1186/s43556-024-00183-1, https://c19p.org/xu13

571 patient metformin prophylaxis study: 62% lower combined mortality/intubation (p=0.03) and 81% lower progression (p=0.003).
Retrospective 571 type 2 diabetes patients with COVID-19 in China, showing lower combined mortality/mechanical ventilation with metformin.

Aug 2023, Diabetes, Metabolic Syndrome and Obesity, https://www.dovepress.com/effects-of-metformin-on-covid-19-patients-with-type-2-diabetes-a-retro-peer-reviewed-fulltext-article-DMSO, https://c19p.org/guo2

39,616 patient metformin prophylaxis study: 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.

Feb 2022, Diabetes Care, https://diabetesjournals.org/care/article/doi/10.2337/dc21-2186/144605/Glycemic-Control-and-Clinical-Outcomes-in-U-S, https://c19p.org/wong2

413 patient metformin prophylaxis study: 81% lower ICU admission (p=0.008), 39% lower progression (p=0.009), and 17% shorter hospitalization (p=0.001).
Retrospective 413 hospitalized COVID-19 patients with type 2 diabetes in China showing lower ICU admission, lower pneumonia incidence, and shorter hospital stay with metformin use.

Jun 2024, Translational Medicine of Aging, https://www.sciencedirect.com/science/article/pii/S2468501124000026, https://c19p.org/chen28

189 patient metformin late treatment RCT: 74% lower mortality (p=0.06), 79% lower ventilation (p=0.05), 63% lower ICU admission (p=0.07), and 5% shorter hospitalization (p=0.52).
RCT 189 hospitalized patients showing lower mortality, ICU admission, and intubation with metformin, statistically significant only for intubation. Treatment patients may have also taken metformin prior to admission. Authors note that patients receiving metformin prior to the study were not matched, and diabetes and hyperlipidemia differed between groups.

Jul 2022, Advanced Pharmaceutical Bulletin, https://apb.tbzmed.ac.ir/Article/apb-33452, https://c19p.org/shaseb

64,349 patient metformin prophylaxis PSM study: 50% lower ventilation (p=0.01) and 51% 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.

Jul 2022, Cell Reports Methods, https://www.sciencedirect.com/science/article/pii/S2667237523001327, https://c19p.org/cousinsmf

1,356 patient metformin prophylaxis study: 74% lower mortality (p=0.03) and 25% lower ventilation (p=0.44).
PSM/IPTW retrospective 1,356 hospitalized COVID-19 patients with type 2 diabetes in China, showing lower mortality/hospice with metformin use.

Mar 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-09639-2, https://c19p.org/ma5

123,709 patient metformin prophylaxis PSM study: 25% lower mortality (p=0.001), 25% lower ventilation (p=0.01), 19% lower ICU admission (p=0.005), and 15% lower hospitalization (p<0.0001).
TriNetX retrospective 123,709 vaccinated patients with type 2 diabetes, showing significantly lower risk of COVID-19 mortality, mechanical ventilation, and hospitalization with metformin use. There was no significant difference for cases. The increasing benefit for more serious outcomes matches the results of studies to date.

May 2023, Diabetes Research and Clinical Practice, https://www.sciencedirect.com/science/article/pii/S0168822723004540, https://c19p.org/yen

metformin prophylaxis study: 44% lower progression (p<0.0001) and 37% lower hospitalization (p<0.0001).
Retrospective 4,944 COVID-19 patients with type 2 diabetes in the USA, showing lower risk of hospitalization and combined ICU/intubation/death with metformin use.

Jun 2022, BMJ Open Diabetes Research & Care, https://drc.bmj.com/content/10/3/e002774.long, https://c19p.org/yeh2

26,508 patient metformin early treatment study: 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 continuation of prophylactic treatment in some cases, and may be early or late treatment in other cases. Further reduction in mortality was seen with combinations of treatments.

Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/huntmf

8,173 patient metformin prophylaxis 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 COVID-19 infection (and continued use). Before included use up to 2 years before, and after included use up to 60 days later.

Dec 2021, BMJ Open, https://bmjopen.bmj.com/content/11/12/e050051.info, https://c19p.org/wallace

131 patient metformin late treatment study: 76% lower mortality (p=0.02).
Retrospective 131 hospitalized COVID-19 patients with type 2 diabetes, showing lower mortality with metformin treatment and acarbose treatment.

Sep 2021, Endocrinology, Diabetes & Metabolism, https://onlinelibrary.wiley.com/doi/10.1002/edm2.301https://onlinelibrary.wiley.com/doi/pdf/10.1002/edm2.301, https://c19p.org/li18

188 patient metformin late treatment study: 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 is essential. Patients that used pre-hospital metformin therapy but interrupted the treatment during hospitalization showed higher mortality than those that continued metformin therapy.

Jul 2021, Diabetology & Metabolic Syndrome, https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-021-00695-8, https://c19p.org/tamura

9,555 patient metformin prophylaxis PSM study: 62% lower mortality (p=0.03), 9% higher ICU admission (p=0.78), and 22% lower hospitalization (p=0.1).
Retrospective 17,396 PCR+ patients in the USA, showing lower mortality with metformin use.

Mar 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26873, https://c19p.org/bramante4

220 patient metformin prophylaxis study: 61% lower mortality (p=0.02).
Retrospective 219 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment.

Jan 2021, Front. Endocrinol., https://www.frontiersin.org/articles/10.3389/fendo.2020.600439/full, https://c19p.org/crouse

283 patient metformin prophylaxis study: 75% lower mortality (p=0.02).
Retrospective 283 COVID-19+ diabetes patients in China, showing lower mortality with existing metformin treatment.

May 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/configurable/content/journals$002ftpmd$002f103$002f1$002farticle-p69.xml?t:ac=journals%24002ftpmd%24002f103%24002f1%24002farticle-p69.xml, https://c19p.org/luo3

131 patient metformin prophylaxis study: 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, suggesting that the result may not be explained by metformin being used early in type II diabetes.

Sep 2020, Endocrine Practice, https://www.endocrinepractice.org/article/S1530-891X(20)48222-9/fulltext, https://c19p.org/li12

624,771 patient metformin prophylaxis study: 34% lower mortality (p<0.0001) and 31% lower hospitalization (p<0.0001).
Retrospective 624,771 people with type 2 diabetes in the UK, showing lower COVID-19 mortality and hospitalization with metformin use.

Sep 2022, Diabetes, Obesity and Metabolism, https://onlinelibrary.wiley.com/doi/10.1111/dom.14872, https://c19p.org/zaccardi

1,307 patient metformin early treatment RCT: 52% lower combined mortality/hospitalization (p=0.09), 40% lower progression (p=0.03), and 37% improved viral clearance (p=0.0008).
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 treatments fluvoxamine and ivermectin. Control arm results are very different between treatments, for example considering hospitalization/death, this was 1.0% for ivermectin vs. 2.7% for overall control, however it was 1.3% for the ivermectin-specific control. 394 control patients are shared. The rate for the non-shared 261 metformin control patients is 5%, compared to 1.3% for ivermectin control patients. The metformin arm started earlier, however it is unclear why the difference in outcomes is so large. Results were delayed for 6 months with no explanation, with followup ending Feb 14, 2022. Adherence was very low, with 77% overall reporting 70+% adherence. Numbers for 100% adherence are not provided. Multiple outcomes are missing, for example time to..

Aug 2022, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2201662, https://c19p.org/covidoutmf

148 patient metformin prophylaxis PSM 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 2021, Diabetes Research and Clinical Practice, https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(20)30876-7/fulltext, https://c19p.org/jiang2

7,539 patient metformin prophylaxis study: 23% lower hospitalization (p=0.004) and 12% fewer cases (p=0.04).
Retrospective 7,539 patients with diabetes mellitus type 2 and chronic kidney disease in Croatia showing lower risk of SARS-CoV-2 infection with SGLT-2 inhibitors, metformin, and repaglinide use, and lower risk of COVID-19 hospitalization with SGLT-2 inhibitors and metformin use.

Mar 2024, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0301056, https://c19p.org/dimnjakovic

137 patient metformin prophylaxis study: 49% lower mortality (p=0.02).
Retrospective 137 hospitalized mild to moderate COVID-19 patients with type 2 diabetes in Indonesia, showing a significantly lower mortality with metformin treatment.

Sep 2023, Folia Medica Indonesiana, https://e-journal.unair.ac.id/FMI/article/view/46944, https://c19p.org/zihono

metformin prophylaxis study: 49% lower mortality (p=0.002).
Retrospective 375 hospitalized diabetes patients in Belgium, showing lower risk of COVID-19 mortality with metformin use.

Dec 2022, Annals of Endocrinology, https://pubmed.ncbi.nlm.nih.gov/37574109/, https://c19p.org/servais

97 patient metformin prophylaxis study: 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 2021, Diabetes & Metabolism, https://www.sciencedirect.com/science/article/pii/S126236362100080X, https://c19p.org/alsalameh

355 patient metformin prophylaxis study: 47% lower mortality (p=0.02).
Retrospective 355 diabetic hospitalized COVID-19 patients in the Philippines, showing lower mortality with metformin use.

Oct 2021, J. the ASEAN Federation of Endocrine Societies, https://www.asean-endocrinejournal.org/index.php/JAFES/article/view/1155, https://c19p.org/ong

240 patient metformin prophylaxis PSM study: 42% lower mortality (p=0.02).
Retrospective 586 diabetic hospitalized COVID-19 patients in Turkey, showing lower mortality with existing metformin use.

Oct 2021, Irish J. Medical Science, https://link.springer.com/article/10.1007/s11845-021-02823-9/fulltext.html, https://c19p.org/saygili

2,794 patient metformin prophylaxis 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 2021, Diabetologia, https://link.springer.com/article/10.1007/s00125-020-05351-w, https://c19p.org/wargny

13,112 patient metformin prophylaxis PSM study: 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.

Jan 2022, Diabetes, Obesity and Metabolism, https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14648, https://c19p.org/ojedafernandez

4,014 patient metformin prophylaxis study: 53% lower combined mortality/ICU admission (p=0.08) and 45% lower hospitalization (p=0.0002).
Retrospective diabetic COVID-19 patients in Italy, showing lower risk of hospitalization with metformin use.

Jun 2023, Nutrition, Metabolism and Cardiovascular Diseases, https://www.sciencedirect.com/science/article/pii/S0939475323002491, https://c19p.org/piarulli

13,585 patient metformin prophylaxis PSM study: 41% lower mortality (p=0.003), 16% higher ventilation (p=0.49), 3% lower ICU admission (p=0.85), and 4% higher hospitalization (p=0.72).
Retrospective 13,585 COVID+ patients in the USA, showing lower mortality with metformin use, but no significant difference for ventilation, ICU admission, and hospitalization.

Oct 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0275787, https://c19p.org/morrison

43,610 patient metformin prophylaxis study: 60% lower mortality (p<0.0001).
UK Biobank retrospective including 43,610 type 2 diabetes patients, showing lower mortality with metformin use within matched type 2 diabetes patients.

May 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.05.19.23290214, https://c19p.org/araldi

191 patient metformin late treatment study: 65% lower mortality (p=0.04).
Retrospective diabetes patients in the UK, showing lower mortality for metformin treatment (administered within 21 days after a positive PCR test).

Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.20.20174169, https://c19p.org/abujamous

metformin prophylaxis study: 38% lower mortality (p=0.02) and 15% lower hospitalization (p=0.25).
Retrospective 54,009 diabetes patients in Italy, showing lower mortality with metformin use.

Oct 2022, Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, https://www.dovepress.com/infection-rates-and-impact-of-glucose-lowering-medications-on-the-clin-peer-reviewed-fulltext-article-DMSOhttps://www.dovepress.com/getfile.php?fileID=84551, https://c19p.org/mannucci

775 patient metformin prophylaxis study: 52% lower mortality (p=0.009).
Retrospective 775 nursing home residents in the USA, showing lower mortality with existing metformin use.

Jan 2021, J. the American Medical Directors Association, https://www.sciencedirect.com/science/article/pii/S1525861020309245, https://c19p.org/lally

733 patient metformin prophylaxis study: 33% lower severe cases (p=0.03).
Retrospective 733 hospitalized COVID-19 patients with diabetes in the USA, showing lower risk of severity with metformin use.

Nov 2022, J. Community Hospital Internal Medicine Perspectives, https://scholarlycommons.gbmc.org/jchimp/vol12/iss6/5, https://c19p.org/milosavljevic

15,968 patient metformin prophylaxis study: 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, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.

Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3mf

189,998 patient metformin prophylaxis study: 22% lower mortality (p=0.001).
Retrospective 224,190 type 2 diabetes patients in Russia, showing lower mortality with metformin use.

Aug 2022, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2022.909874/full, https://c19p.org/shestakova

75 patient metformin prophylaxis study: 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 2022, J. Thrombosis and Thrombolysis, https://link.springer.com/article/10.1007%2Fs11239-022-02631-7, https://c19p.org/usman

28,093 patient metformin prophylaxis study: 39% lower hospitalization (p=0.04).
Retrospective 28,093 COVID+ patients in the USA, showing lower risk of hospitalization with metformin use.

Sep 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-96720-x, https://c19p.org/ando

2,851,465 patient metformin prophylaxis study: 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 diabetes.

Mar 2021, The Lacent Diabetes & Endocrinology, https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00050-4/fulltext, https://c19p.org/khunti

235 patient metformin prophylaxis study: 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.

Aug 2020, Diabetes & Metabolism J., https://www.e-dmj.org/journal/view.php?doi=10.4093/dmj.2020.0146, https://c19p.org/kim3

80 patient metformin prophylaxis study: 72% improved recovery (p=0.03).
Retrospective 108 T2D patients hospitalized with COVID-19, showing lower risk of unfavorable outcomes with metformin use vs. other diabetic medications.

Jan 2022, Int. J. Endocrinology, https://www.hindawi.com/journals/ije/2022/9322332/, https://c19p.org/fu

64,892 patient metformin prophylaxis study: 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.

Oct 2021, Diabetes Care, https://care.diabetesjournals.org/content/early/2021/10/06/dc21-1351.article-info, https://c19p.org/wander

22,124 patient metformin prophylaxis study: 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.

Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.22.21254110, https://c19p.org/alamgir

3,136 patient metformin prophylaxis study: 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 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.08.29.22279355, https://c19p.org/chan

917,198 patient metformin late treatment study: 44% lower mortality (p<0.0001).
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..

Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizimf

109 patient metformin prophylaxis study: 50% lower mortality (p=0.01).
Retrospective 109 hospitalized COVID-19 patients in Syria, 68 with diabetes, showing significantly lower mortality with metformin vs. sulfonylureas, and significantly higher mortality with discontinuation of metformin.

Nov 2023, Research J. Pharmacy and Technology, https://www.rjptonline.org/HTMLPaper.aspx?Journal=Research%20Journal%20of%20Pharmacy%20and%20Technology;PID=2023-16-11-25, https://c19p.org/mamari

16,504 patient metformin prophylaxis study: 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.

Sep 2021, BMJ Open Diabetes Research & Care, https://drc.bmj.com/content/9/1/e002299.abstract, https://c19p.org/wang5

9,531 patient metformin prophylaxis study: 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 2021, Diabetes Therapy, https://link.springer.com/article/10.1007/s13300-021-01110-1/fulltext.html, https://c19p.org/boye

100 patient metformin prophylaxis study: 78% lower mortality (p=0.01) and 41% improved recovery (p=0.0002).
Prospective study of 60 hospitalized type 2 diabetes patients with COVID-19 on metformin monotherapy compared to 40 patients on other diabetes treatments, showing significantly lower inflammatory biomarkers, oxidative stress, and mortality, and improvements in radiological and clinical outcomes with metformin. Confounding due to differences in baseline characteristics may be significant.

Nov 2023, European Review for Medical and Pharmacological Sciences, https://doi.org/10.26355/eurrev_202312_34583, https://c19p.org/alkuraishy3

1,090 patient metformin prophylaxis PSM study: 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 HbA1c, eGFR, and diabetes duration, but have a lower number of patients. CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes).

Dec 2020, Diabetes & Metabolism, https://www.sciencedirect.com/science/article/pii/S1262363620302731, https://c19p.org/lalau

179 patient metformin prophylaxis 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 2021, GeroScience, https://link.springer.com/article/10.1007/s11357-021-00397-z, https://c19p.org/blanc

90 patient metformin prophylaxis study: 45% lower mortality (p=0.1).
Retrospective 90 hospitalized COVID-19 patients with diabetes in Italy, showing lower mortality with metformin use, without statistical significance.

Oct 2020, Diabetes Care, https://diabetesjournals.org/care/article/43/12/3042/30894/Impact-of-Comorbidities-and-Glycemia-at-Admission, https://c19p.org/mirani

58 patient metformin prophylaxis study: 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.

Jul 2020, J. Hematology & Oncology, https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00934-x, https://c19p.org/wang3

421 patient metformin early treatment RCT: 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 [doyourownresearch.substack.com]. 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 hospitalization must be between 24 and 32. However, authors report 34 events for ER/hospitalization. RCT with 215 patients treated with metformin and 203 controls, showing no significant difference with treatment. For multiple major issues with this trial see [doyourownresearch.substack.com, doyourownresearch.substack.com]. An expression of concern was posted in 2024 [thelancet.com]. The hospitalization risk for off-protocol patients was several times higher in both arms, resulting in Simpson's paradox when combining per-protocol and off-protocol patients [twitter.com]. 750mg twice daily for 10 days.

Aug 2021, The Lancet Regional Health - Americas, https://www.sciencedirect.com/science/article/pii/S2667193X21001381, https://c19p.org/reis3

524 patient metformin prophylaxis study: 29% lower mortality (p=0.5).
Retrospective 524 hospitalized COVID-19 patients with diabetes in Italy, showing lower risk of mortality with metformin use, without statistical significance. The results adjusted only for COVID-19 MRS differ between the text and Figure 2.

Mar 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/7/1874, https://c19p.org/silverii

430 patient metformin prophylaxis study: 23% lower mortality (p=0.15).
Retrospective 430 hospitalized COVID-19 patients with type 2 diabetes in Poland showing lower mortality with metformin and higher mortality with remdesivir, convalescent plasma, and aspirin in univariable analysis. These results were not statistically significant except for aspirin, and no baseline information per treatment is provided to assess confounding.

Mar 2024, Biomedicines, https://www.mdpi.com/2227-9059/12/3/605, https://c19p.org/lewandowski

132 patient metformin prophylaxis study: 37% lower ICU admission (p=0.24).
Mouse models showing reduced lung and kidney injury with metformin. Metformin minimized lung damage and fibrosis in a mouse model of LPS-induced ARDS, and reduced UUO and FAN-induced kidney fibrosis. In Vitro study showing that metformin increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis, and inflammation markers in lung epithelial cells. Authors also include a retrospective study showing lower ICU admission with metformin without statistical significance.

Nov 2023, Redox Biology, https://www.sciencedirect.com/science/article/pii/S2213231723003580, https://c19p.org/miguel

247 patient metformin prophylaxis study: 37% lower mortality (p=0.13).
Retrospective 247 hospitalized COVID-19 diabetes patients, showing lower mortality with metformin use in unadjusted results.

Dec 2020, Diabetes, Obesity and Metabolism, https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.14256, https://c19p.org/sourij

120 patient metformin prophylaxis study: 33% lower mortality (p=0.46).
Retrospective 120 COVID-19 diabetes patients, showing non-statistically significantly lower mortality with existing metformin treatment.

Jul 2020, Diabetes Care, https://care.diabetesjournals.org/content/43/7/1399, https://c19p.org/chen3

1,317 patient metformin prophylaxis study: 20% lower mortality (p=0.46).
Analysis of 1,317 hospitalized COVID-19 patients with diabetes showing lower mortality with metformin use, without statistical significance.

May 2020, Diabetologia, https://link.springer.com/10.1007/s00125-020-05180-x, https://c19p.org/cariou

3,974,272 patient metformin prophylaxis study: 3% lower hospitalization (p=0.004).
Retrospective 3,974,272 COVID-19 patients in the USA, showing 3% lower risk of hospitalization with pre-existing metformin use.

Mar 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0282961, https://c19p.org/sandhu2

43 patient metformin prophylaxis study: 15% lower severe cases (p=0.05).
Retrospective 43 diabetes patients hospitalized for COVID-19 in Italy, showing lower risk of severe cases with metformin vs. insulin.

Jan 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/1/145, https://c19p.org/pinchera

75 patient metformin prophylaxis study: 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.

Nov 2021, Circulation, 144:A12228, https://www.ahajournals.org/doi/abs/10.1161/circ.144.suppl_1.12228, https://c19p.org/bliden

7,047 patient metformin prophylaxis study: 19% lower PASC (p=0.29).
Retrospective 7,047 outpatients with type 2 diabetes showing a lower risk of PASC (long COVID) with metformin compared to sulfonylurea or DPP-4 inhibitor use, without statistical significance.

May 2024, Clinical Epidemiology, https://www.dovepress.com/risk-of-post-acute-sequelae-of-sars-cov-2-infection-pasc-among-patient-peer-reviewed-fulltext-article-CLEP, https://c19p.org/olawore

12,331 patient metformin prophylaxis PSM study: 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.

Sep 2022, SSRN Electronic J., https://www.ssrn.com/abstract=4225660, https://c19p.org/yip2

6,256 patient metformin prophylaxis study: 12% lower mortality (p=0.65).
Retrospective 6,256 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment, statistically significant only for women.

Dec 2020, The Lancet Healthy Longevity, https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(20)30033-7/fulltext, https://c19p.org/bramante

11,892 patient metformin prophylaxis 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.

Feb 2021, Acta Diabetologica, https://link.springer.com/article/10.1007%2Fs00592-020-01666-7, https://c19p.org/oh

44,977 patient metformin prophylaxis study: 22% lower hospitalization (p=0.11).
Retrospective 76,764 diabetes patients in Italy, showing that patients on metformin had lower rates of COVID-19 hospitalization compared to those on insulin/insulin secretagogues, GLP-1 receptor agonists, and DPP-4 inhibitors. Metformin vs. no metformin results are not provided. The most relevant result for COVID-19 and metformin may be the DPP-4i comparison, based on the DPP-4i group being the most similar to the metformin group in terms of baseline COVID-19 risk and confounders. Patients on insulin/secretagogues may have more severe or advanced diabetes.

Aug 2023, Biomedicines, https://www.mdpi.com/2227-9059/11/8/2292, https://c19p.org/greco

4,462 patient metformin prophylaxis PSM study: 1% lower mortality (p=0.91) and 5% shorter hospitalization (p=0.23).
Retrospective 4,462 COVID+ diabetes patients in the USA, showing no significant difference in outcomes with metformin use.

Nov 2022, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2022.1002834/full, https://c19p.org/miao

16,043 patient metformin prophylaxis study: 10% lower mortality (p=0.19) and 8% lower combined mortality/hospitalization (p=0.12).
Retrospective 31,006 diabetic COVID-19 patients in Spain, showing lower mortality with metformin treatment, without statistical significance. Authors provide results for metformin compared with untreated patients rather than all non-metformin patients, which may increase confounding due to higher prevalence for treatment of patients with more severe disease.

Oct 2022, Primary Care Diabetes, https://www.sciencedirect.com/science/article/pii/S175199182200167X, https://c19p.org/ouchi

366 patient metformin prophylaxis study: 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.

May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.20.21255792v2, https://c19p.org/ravindra

763 patient metformin prophylaxis study: 15% lower hospitalization (p=0.56).
Retrospective 763 COVID-19 patients with type 2 diabetes in Uzbekistan, showing lower hospitalization with metformin use in unadjusted results, without statistical significance.

Jun 2023, Obesity and metabolism, https://www.omet-endojournals.ru/jour/article/view/12801, https://c19p.org/alieva

metformin prophylaxis study: 1% fewer cases (p=0.45).
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of metformin.

Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenmf

790 patient metformin prophylaxis study: 1% lower mortality (p=0.78).
Retrospective 790 hospitalized type 2 diabetes patients ≥80 years old in Spain, showing no significant difference in mortality with existing metformin use.

Dec 2020, Research Square, https://www.researchsquare.com/article/rs-133358/v1, https://c19p.org/ramosrincon

354 patient metformin prophylaxis study: 37% lower mortality (p=0.12), 39% higher ICU admission (p=0.26), and 3% higher ARDS (p=0.92).
Prospective multicenter study of 354 hospitalized type 2 diabetes patients with COVID-19 in Greece showing increased risk with DPP4 inhibitor use as part of chronic diabetes treatment. There was no significant difference with metformin use in unadjusted results. Results do not account for differences in the risk of hospitalization.

May 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/6/1416, https://c19p.org/akinosoglou

406 patient metformin prophylaxis study: 10% lower severe cases (p=0.53).
Retrospective 406 COVID-19 patients in Iran, showing lower risk of severe cases with metformin use in unadjusted results, without statistical significance.

Oct 2023, Cureus, https://www.cureus.com/articles/194481-development-of-a-scoring-method-based-on-a-chest-ct-scan-to-determine-the-outcomes-of-covid-19-patients, https://c19p.org/bidari

1,039 patient metformin prophylaxis study: 3% more cases (p=0.87).
Retrospective 1,039 diabetes patients in Jordan, showing no significant difference in COVID-19 cases with metformin use in unadjusted results. Severity outcomes are not provided for metformin.

Sep 2023, J. Int. Medical Research, http://journals.sagepub.com/doi/10.1177/03000605231198413, https://c19p.org/farah

15,227 patient metformin prophylaxis study: 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. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtmf

44,046 patient metformin prophylaxis study: 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 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2mf

498 patient metformin prophylaxis PSM 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 2020, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01832-2, https://c19p.org/perezbelmonte

529 patient metformin prophylaxis study: 1% higher mortality (p=0.98), 4% higher ventilation (p=0.87), and 8% lower ICU admission (p=0.72).
Retrospective 529 hospitalized COVID-19 patients with type 2 diabetes, showing no significant difference in outcomes with metformin use. This does not account for the different risk of being hospitalized based on metformin use. Authors note that "there is a lower-than-expected proportion of metformin prescription in our population (28%) compared to the general US population", without noting that this may reflect the lower risk of being hospitalized for metformin patients, as shown in other studies [c19early.org].

Jun 2023, Endocrine Practice, https://www.sciencedirect.com/science/article/pii/S1530891X23004299, https://c19p.org/obiriyeboah

103 patient metformin prophylaxis study: 16% higher mortality (p=0.46) and 16% higher severe cases (p=0.46).
Analysis of 103 elderly hospitalized COVID-19 patients in Spain, showing higher mortality with metformin, without statistical significance.

Apr 2021, Gerontology, https://www.karger.com/Article/FullText/515159, https://c19p.org/galvezbarronmf

1,213 patient metformin prophylaxis PSM study: 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.

Aug 2021, Cell Metabolism, https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30426-5, https://c19p.org/cheng2

110 patient metformin prophylaxis study: 225% higher progression (p=0.05).
Retrospective 110 hospitalized COVID-19 patients with diabetes in China, showing increased risk of severity with metformin.

Oct 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.12897, https://c19p.org/gao4

72 patient metformin prophylaxis PSM study: 120% higher progression (p=0.26).
Retrospective 293 patients in South Korea, showing higher risk of progression with metformin use, without statistical significance.

Jun 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/6/1959, https://c19p.org/choi2mf
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