Summary of COVID-19 metformin studies

1. Ventura-López et al., Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial

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

2. Wong et al., 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

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

3. Ghany et al., Metformin is associated with lower hospitalizations, mortality and severe coronavirus infection among elderly medicare minority patients in 8 states in USA

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

4. Jang et al., Impact of Antidiabetic Drugs on Clinical Outcomes of COVID-19: A Nationwide Population-Based Study

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

5. Xu et al., Effects of different treatments for type 2 diabetes mellitus on mortality of coronavirus disease from 2019 to 2021 in China: a multi-institutional retrospective study

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

6. Guo et al., Effects of Metformin on COVID-19 Patients with Type 2 Diabetes: A Retrospective Study

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

7. Wong et al., Glycemic Control and Clinical Outcomes in U.S. Patients With COVID-19: Data From the National COVID Cohort Collaborative (N3C) Database

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

8. Chen et al., Metformin alleviates inflammatory response and severity rate of COVID-19 infection in elderly individuals

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

9. Shaseb et al., Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19

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

10. Cousins et al., Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19

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

11. Ma et al., Metformin is associated with favorable outcomes in patients with COVID-19 and type 2 diabetes mellitus

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

12. Yen et al., Metformin use before COVID-19 vaccination and the risks of COVID-19 incidence, medical utilization, and all-cause mortality in patients with type 2 diabetes mellitus

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

13. Yeh et al., Hospitalization and mortality in patients with COVID-19 with or at risk of type 2 diabetes: data from five health systems in Pennsylvania and Maryland

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

14. Hunt et al., Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans

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

15. Wallace et al., Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study

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

16. Li et al., Inpatient use of metformin and acarbose is associated with reduced mortality of COVID-19 patients with type 2 diabetes mellitus

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

17. Tamura et al., Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies

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

18. Bramante et al., Outpatient metformin use is associated with reduced severity of COVID‐19 disease in adults with overweight or obesity

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

19. Crouse et al., Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes

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

20. Luo et al., Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis

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

21. Li et al., Metformin Use in Diabetes Prior to Hospitalization: Effects on Mortality in Covid-19

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

22. Zaccardi et al., Ethnicity and risks of severe COVID-19 outcomes associated with glucose-lowering medications: A cohort study

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

23. Sugimoto et al., Biguanides Associate with Decreased Early Mortality and Risk of Acute Kidney Injury In Hospitalized COVID-19 Patients: a nationwide retrospective cohort study in Japan

168,550 patient metformin late treatment study: 40% lower mortality (p<0.0001).
Retrospective 168,370 hospitalized COVID-19 patients with diabetes in Japan showing lower mortality and reduced risk of acute kidney injury with biguanide (likely primarily or only metformin) use. Authors hypothesize that metformin's activation of AMPK in renal tubular epithelium may provide a protective effect against COVID-19-induced kidney damage.
Jul 2024, medRxiv, https://www.medrxiv.org/content/10.1101/2024.07.20.24310736v1, https://c19p.org/sugimoto

24. Bramante et al., Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19

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

25. Jiang et al., Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: A retrospective cohort study

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

26. Dimnjaković et al., Association of anti-diabetic drugs and covid-19 outcomes in patients with diabetes mellitus type 2 and chronic kidney disease: Nationwide registry analysis

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

27. Zihono et al., Metformin Effectiveness in Reducing Mortality among Covid-19 Patients with Type 2 Diabetes Mellitus at a Tertiary Hospital in Indonesia

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

28. Servais et al., Mortality-related risk factors of inpatients with diabetes and COVID-19: a multicenter retrospective study in Belgium

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

29. Al-Salameh et al., The association between metformin treatment and COVID-19 outcomes according to metformin continuation during hospitalisation

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

30. Ong et al., Association Between Metformin Use and Mortality Among Patients with Type 2 Diabetes Mellitus Hospitalized for COVID-19 Infection

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

31. Saygili et al., Preadmission usage of metformin and mortality in COVID-19 patients including the post-discharge period

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

32. Wargny et al., Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study

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

33. Ojeda-Fernández et al., Metformin use is associated with a decrease in risk of hospitalization and mortality in COVID-19 diabetic patients: a population-based study in Lombardy

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

34. Piarulli et al., Association of renin-angiotensin-aldosterone system inhibitors with best COVID-19 outcomes in a diabetic population of the Veneto Region (north-east Italy): a lesson for endemic phase?

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

35. Morrison et al., COVID-19 outcomes in patients taking cardioprotective medications

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

36. Araldi et al., Effects of antidiabetic drugs on mortality risks in individuals with type 2 diabetes: A prospective cohort study of UK Biobank participants

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

37. Abu-Jamous et al., Associations of comorbidities and medications with COVID-19 outcome: A retrospective analysis of real-world evidence data

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

38. Mannucci et al., Infection Rates and Impact of Glucose Lowering Medications on the Clinical Course of COVID-19 in People with Type 2 Diabetes: A Retrospective Observational Study

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

39. Lally et al., Metformin is Associated with Decreased 30-Day Mortality Among Nursing Home Residents Infected with SARS-CoV2

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

40. Milosavljevic et al., Evaluation of Glycemic Control and Predictors of Severe Illness and Death in Patients With Diabetes Hospitalized With COVID-19

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

41. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments

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

42. Shestakova et al., 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

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

43. Usman et al., Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes

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

44. Ando et al., Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States

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

45. Khunti et al., Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England

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

46. Kim et al., The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea

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

47. Fu et al., Prognostic Factors for COVID-19 Hospitalized Patients with Preexisting Type 2 Diabetes

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

48. Wander et al., Prior Glucose-Lowering Medication Use and 30-Day Outcomes Among 64,892 Veterans With Diabetes and COVID-19

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

49. Alamgir et al., Drug repositioning candidates identified using in-silico quasi-quantum molecular simulation demonstrate reduced COVID-19 mortality in 1.5M patient records

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

50. Chan et al., Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes

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

51. Mehrizi et al., Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data

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

52. Mamari et al., The effect of Chronic treatments of Type 2-diabetes mellitus on COVID-19 Morbidity and Symptoms Severity

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

53. Wang et al., Evaluation and management of COVID-19-related severity in people with type 2 diabetes

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

54. Boye et al., 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

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

55. Al-kuraishy et al., The potential therapeutic effect of metformin in type 2 diabetic patients with severe COVID-19

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

56. Lalau et al., Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19

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

57. Blanc et al., Therapeutic prevention of COVID-19 in elderly: a case–control study

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

58. Mirani et al., Impact of Comorbidities and Glycemia at Admission and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes With COVID-19: A Case Series From an Academic Hospital in Lombardy, Italy

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

59. Wang et al., A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward

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

60. Reis et al., Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial

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 [web.archive.org]. 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

61. Hussein et al., The Proportion and Associated Factors for Mortality among COVID-19 Infection with Diabetes in Iraq

545 patient metformin prophylaxis study: 64% lower mortality (p=0.05).
Retrospective 545 hospitalized COVID-19 patients with diabetes showing high mortality (33%). Metformin, SGLT inhibitors, and DPP4 inhibitors were associated with lower mortality compared with insulin.
Jun 2024, The Review of Diabetic Studies, https://diabeticstudies.org/menuscript/index.php/RDS/article/view/393, https://c19p.org/hussein3

62. Silverii et al., Is Metformin Use Associated with a More Favorable COVID-19 Course in People with Diabetes?

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

63. Lewandowski et al., Insulin and Metformin Administration: Unravelling the Multifaceted Association with Mortality across Various Clinical Settings Considering Type 2 Diabetes Mellitus and COVID-19

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

64. Miguel et al., Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney

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

65. Sourij et al., COVID‐19 fatality prediction in people with diabetes and prediabetes using a simple score upon hospital admission

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

66. Chen et al., Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication

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

67. Cariou et al., Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study

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

68. Sandhu et al., Outpatient medications associated with protection from COVID-19 hospitalization

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

69. Pinchera et al., Diabetes and SARS-CoV-2 Infection: The Potential Role of Antidiabetic Therapy in the Evolution of COVID-19

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

70. Bliden et al., Metformin Use in Patients Hospitalized With COVID-19: Lower Inflammation, Oxidative Stress, and Thrombotic Risk Markers and Better Clinical Outcomes

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

71. Olawore et al., Risk of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Among Patients with Type 2 Diabetes Mellitus on Anti-Hyperglycemic Medications

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

72. Yip et al., Metformin Does Not Reduce Hospitalisation for COVID-19

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

73. Bramante et al., Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis

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

74. Oh et al., Metformin use and risk of COVID-19 among patients with type II diabetes mellitus: an NHIS-COVID-19 database cohort study

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

75. Greco et al., The Impact of GLP-1 RAs and DPP-4is on Hospitalisation and Mortality in the COVID-19 Era: A Two-Year Observational Study

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

76. Miao et al., Metformin use and mortality and length of stay among hospitalized patients with type 2 diabetes and COVID-19: A multiracial, multiethnic, urban observational study

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

77. Ouchi et al., Antidiabetic treatment and COVID-19 Outcomes: A population-based cohort study in primary health care in Catalonia during the first wave of the pandemic

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

78. Ravindra et al., Retrospective Assessment of Treatments of Hospitalized Covid-19 Patients

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

79. Alieva et al., Factors influencing the severity of COVID-19 course for patients with diabetes mellitus in tashkent: a retrospective cohort study

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

80. MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications

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

81. Goodall et al., Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study

981 patient metformin prophylaxis study: 3% lower mortality (p=0.81).
Retrospective 981 hospitalized patients in the UK, showing no significant difference with metformin use.
Oct 2020, Epidemiology and Infection, https://www.cambridge.org/core/journals/epidemiology-and-infection/article/risk-factors-for-severe-disease-in-patients-admitted-with-covid19-to-a-hospital-in-london-england-a-retrospective-cohort-study/9B704FF68359D8413E194D7123E49123, https://c19p.org/goodall

82. Ramos-Rincón et al., Association between prior cardiometabolic therapy and in-hospital mortality in very old patients with type 2 diabetes mellitus hospitalized due to COVID-19. A nationwide observational study in Spain

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

83. Akinosoglou et al., COVID-19 Outcomes and Diabetes Mellitus: A Comprehensive Multicenter Prospective Cohort Study

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

84. Bidari et al., Development of a Scoring Method Based on a Chest CT Scan to Determine the Outcomes of COVID-19 Patients

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

85. Farah et al., Prevalence and risk factors of COVID-19 infection, mortality, and post-infection lung fibrosis in patients with type 2 diabetes: a cross-sectional study

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

86. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)

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

87. Huh et al., Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea

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

88. Pérez-Belmonte et al., 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

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

89. Obiri-Yeboah et al., Association of metformin, dipeptidyl dipeptidase-4 inhibitors, and insulin with COVID-19-related hospital outcomes in patients with type 2 diabetes

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

90. Gálvez-Barrón et al., COVID-19: Clinical Presentation and Prognostic Factors of Severe Disease and Mortality in the Oldest-Old Population: A Cohort Study

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

91. Cheng et al., Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes

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

92. Gao et al., Risk of Metformin in Patients With Type 2 Diabetes With COVID-19: A Preliminary Retrospective Report

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

93. Choi et al., Clinical Characteristics and Disease Progression in Early-Stage COVID-19 Patients in South Korea

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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