Metformin for COVID-19: real-time analysis of 138 studies

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Metformin for COVID-19

105 studies with >300,000 patients

Control Serious Outcome Risk

Metformin

Significantly lower risk for mortality, ventilation, ICU, hospitalization, progression, and recovery.

69 studies from 63 independent teams in 22 countries show significant benefit.

COVID-19 Metformin studies. May 2025. c19early.org

Most studies analyze existing use with diabetic patients. Prophylaxis results typically include continuing use after infection and hospitalization, and greater benefit is seen for more serious outcomes. Recent:

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Granvik.


May 24	Covid Analysis	Metformin reduces COVID-19 risk: real-time meta analysis of 105 studies
	Significantly lower risk is seen for mortality, ventilation, ICU admission, hospitalization, progression, and recovery. 69 studies from 63 independent teams in 22 countries show significant benefit. Meta analysis using the most serious ou..
Apr 11	Johnson et al., Journal of Clinical and Translational Science, doi:10.1017/cts.2024.1162	Is PHASTR faster? A target trial emulation case study in the N3C
	53% lower PASC (p=0.02). N3C target trial emulation study with 9,660 adult COVID-19 patients, showing metformin associated with lower risk of long COVID or death.
Apr 8	Joshi et al., Clinical and Translational Medicine, doi:10.1002/ctm2.70275	Severe SARS‐CoV‐2 infection in diabetes was rescued in mice supplemented with metformin and/or αKG, and patients taking metformin, via HIF1α‐IFN axis
	In Vitro and mouse study showing that metformin and/or alpha-ketoglutarate (αKG) supplementation reduces SARS-CoV-2 infection severity in diabetic mice by modulating the HIF1α–interferon axis. Diabetic mice exhibited elevated viral loads,..
Mar 4	Granvik et al., medRxiv, doi:10.1101/2025.02.28.25323075	Identifying DNA Methylation Patterns in Post COVID-19 Condition: Insights from a One-Year Prospective Cohort Study
	Prospective cohort study with 22 Post COVID-19 condition (PCC+) patients and 22 matched COVID-19 convalescents (PCC-), showing distinct DNA methylation patterns diminishing over time. The study identified TXNRD1 methylation changes associ..
Feb 21	Monsalve et al., Journal of Translational Autoimmunity, doi:10.1016/j.jtauto.2025.100280	NETosis: A key player in autoimmunity, COVID-19, and long COVID
	Review of neutrophil extracellular traps (NETs) and their role in autoimmunity, COVID-19, and long COVID. Authors explain that NETosis is a process where neutrophils release web-like structures (NETs) containing DNA, proteases, and enzyme..
Feb 4	Soff et al., BMJ Open Diabetes Research & Care, doi:10.1136/bmjdrc-2024-004536	Association of glycemic control with Long COVID in patients with type 2 diabetes: findings from the National COVID Cohort Collaborative (N3C)
	18% lower PASC (p=0.001). Retrospective 7,430 COVID-positive patients with type 2 diabetes showing lower risk of long COVID or death with metformin use, and higher risk with insulin use.
Jan 31	Tavares et al., Biophysica, doi:10.3390/biophysica5010004	Investigation of Interactions Between the Protein MPro and the Vanadium Complex VO(metf)2∙H2O: A Computational Approach for COVID-19 Treatment
	In Silico study showing that the vanadium complex VO(metf)2∙H2O (VC) and metformin (MF) may be beneficial for COVID-19 treatment by interacting with the main protease (M^pro) of SARS-CoV-2. Using docking simulations, authors found that VC ..
Jan 29	Bramante et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofae631.016	Metformin reduces the risk of Long COVID or Death over 6 months in an Emulated Target Trial of Primarily Omicron-infected Adults without Diabetes or Prediabetes: a New-User, Active-Comparator Analysis Using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database. This research was supported in part by the Intramural/Extramural research program of the National Center for Advancing Translational Science, NIH
	Emulated target trial of Omicron-infected outpatients without diabetes or prediabetes, showing significantly lower long COVID or death with metformin treatment.
Jan 14	Bramante et al., medRxiv, doi:10.1101/2025.01.13.25320485	Metformin on Time to Sustained Recovery in Adults with COVID-19: The ACTIV-6 Randomized Clinical Trial
	24% higher progression (p=0.28) and 4% worse recovery (p=0.28). RCT 2,991 outpatient adults with mild to moderate COVID-19 showing no significant difference in time to sustained recovery with metformin compared to placebo. Median days to symptom resolution was 9 days vs. 10 days for placebo, without s..
Jan 11	Benfathallah et al., Cureus, doi:10.7759/cureus.77288	Does the Consumption of Metformin Correlate With a Reduction in Mortality Among Patients With Type 2 Diabetes and COVID-19 in Morocco?
	54% lower mortality (p=0.04). Retrospective 115 hospitalized type 2 diabetes patients in Morocco showing significantly lower mortality with metformin use.
Jan 6	Keels et al., Frontiers in Endocrinology, doi:10.3389/fendo.2024.1482853	Antidiabetic agent use and clinical outcomes in patients with diabetes hospitalized for COVID-19: a systematic review and meta-analysis
	59% lower mortality (p=0.002). Systematic review and meta-analysis of 35 studies showing lower mortality with metformin and DPP-4 inhibitor treatment for COVID-19 patients with diabetes.
Dec 18 2024	Halabitska et al., Viruses, doi:10.3390/v16121938	Metformin in Antiviral Therapy: Evidence and Perspectives
	Review of metformin as a promising broad-spectrum antiviral agent, focusing on its potential for treating SARS-CoV-2 infection. Authors highlight metformin's ability to activate AMPK and inhibit mTOR signaling, which can help reduce hyper..
Dec 11 2024	Matviichuk et al., Frontiers in Endocrinology, doi:10.3389/fendo.2024.1459171	Unveiling risk factors for post-COVID-19 syndrome development in people with type 2 diabetes
	5% higher PASC (p=0.64). Retrospective 469 patients with type 2 diabetes in Ukraine showing no significant difference in post-COVID-19 syndrome (PCS) with metformin. There was higher risk with insulin analogs, but lower risk with human insulin.
Nov 30 2024	He et al., IJC Heart & Vasculature, doi:10.1016/j.ijcha.2024.101574	Clinical characteristics and risk factors for in-hospital mortality of COVID-19 patients in Hubei Province: A multicenter retrospective study
	74% lower mortality (p<0.0001). Retrospective 53,030 COVID-19 patients from 138 hospitals in Hubei, China showing lower mortality with metformin.
Nov 29 2024	Chertok Shacham et al., Diabetes and Vascular Disease Research, doi:10.1177/14791641241288390	Impact of blood glucose control on clinical outcomes in type 2 diabetes patients hospitalized with COVID-19 infection
	70% lower mortality (p=0.01). Retrospective 857 hospitalized type 2 diabetes patients showing lower mortality with pre-admission metformin use. Authors report no significant difference in mortality with in-hospital metformin use, but do not report the actual result.
Nov 9 2024	Somasundaram et al., Annals of Medicine, doi:10.1080/07853890.2024.2425829	Metformin use and its association with various outcomes in COVID-19 patients with diabetes mellitus: a retrospective cohort study in a tertiary care facility
	89% lower mortality (p<0.0001). Retrospective 421 hospitalized COVID-19 patients with type 2 diabetes in India, showing significantly lower mortality with metformin use compared to other antidiabetic medications.
Sep 27 2024	Sakamaki et al., Discover Public Health, doi:10.1186/s12982-024-00225-7	Insights from a multicenter nationwide cohort analysis in Japan on the association of underlying conditions and pharmacological interventions with COVID-19 disease severity
	23% lower severe cases (p<0.0001). Retrospective 650,317 COVID-19 patients in Japan showing lower risk of severe COVID-19 with metformin use.
Sep 19 2024	Harmon et al., Journal of General Internal Medicine, doi:10.1007/s11606-024-08864-x	Preadmission Metformin Use Is Associated with Reduced Mortality in Patients with Diabetes Mellitus Hospitalized with COVID-19
	18% lower mortality (p<0.0001). Retrospective 11,993 hospitalized COVID-19 patients with diabetes mellitus but without chronic kidney disease or need for hemodialysis, showing lower mortality with metformin use.
Sep 17 2024	Johnson et al., Diabetes Care, doi:10.2337/DCa24-0032	Prevalent Metformin Use in Adults With Diabetes and the Incidence of Long COVID: An EHR-Based Cohort Study From the RECOVER Program
	N3C/PCORnet retrospective adults with type 2 diabetes in the USA showing lower incidence of mortality or long COVID with metformin use.
Jul 21 2024	Sugimoto et al., medRxiv, doi:10.1101/2024.07.20.24310736	Biguanides Associate with Decreased Early Mortality and Risk of Acute Kidney Injury In Hospitalized COVID-19 Patients: a nationwide retrospective cohort study in Japan
	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 acti..
Jun 30 2024	Hussein et al., The Review of Diabetic Studies, doi:10.1900/RDS.2024.20.12	The Proportion and Associated Factors for Mortality among COVID-19 Infection with Diabetes in Iraq
	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 8 2024	Chen et al., Translational Medicine of Aging, doi:10.1016/j.tma.2024.04.001	Metformin alleviates inflammatory response and severity rate of COVID-19 infection in elderly individuals
	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.
May 31 2024	Chang et al., Biomedicines, doi:10.3390/biomedicines12061223	SARS-CoV-2 Spike Protein 1 Causes Aggregation of α-Synuclein via Microglia-Induced Inflammation and Production of Mitochondrial ROS: Potential Therapeutic Applications of Metformin
	In Vitro and rat study showing that the SARS-CoV-2 spike protein S1 subunit causes aggregation of α-synuclein and microglial activation, which may contribute to the neurological symptoms seen in long COVID. In rats, intranasal administrat..
May 31 2024	Olawore et al., Clinical Epidemiology, doi:10.2147/CLEP.S458901	Risk of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Among Patients with Type 2 Diabetes Mellitus on Anti-Hyperglycemic Medications
	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 30 2024	Hou et al., Scientific Reports, doi:10.1038/s41598-024-63081-0	Metformin is a potential therapeutic for COVID-19/LUAD by regulating glucose metabolism
	In Silico and In Vitro study showing metformin as a potential therapeutic for COVID-19/LUAD by regulating glucose metabolism. Authors identified PTEN and mTOR as potential core target genes of metformin for treating COVID-19/LUAD. Bioinfo..
May 17 2024	Xu et al., Molecular Biomedicine, doi:10.1186/s43556-024-00183-1	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
	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 10 2024	Plowman et al., International Journal of Molecular Sciences, doi:10.3390/ijms25105190	Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review
	Review of the potential of metformin for preventing inflammatory complications and infectious diseases including COVID-19. Authors discuss evidence from preclinical and clinical studies suggesting metformin may help prevent symptoms of CO..
Apr 29 2024	Song et al., Therapeutic Innovation & Regulatory Science, doi:10.1007/s43441-024-00633-6	The Effect of Antihyperglycemic Medications on COVID-19: A Meta-analysis and Systematic Review from Observational Studies
	34% lower mortality (p<0.0001), 35% lower severe cases (p=0.002), and 23% lower hospitalization (p=0.02). Meta analysis of 56 studies showing lower mortality and hospitalization with metformin, GLP-1 receptor agonists, and SGLT-2 inhibitors in COVID-19 patients with type 2 diabetes, while insulin was associated with increased risks.
Apr 16 2024	Agamah et al., ScienceOpen, doi:10.58647/DRUGARXIV.PR000010.v1	Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases
	In Silico study identifying potential drugs beneficial for COVID-19 by integrating transcriptomics, proteomics, metabolomics, lipidomics, and drug data. Authors explore interactions between drugs, molecular features, and disease severity...
Apr 5 2024	Lockwood, T., BioMetals, doi:10.1007/s10534-024-00590-5	Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent
	In Silico analysis suggesting potential benefits of metformin and zinc for COVID-19. Author proposes that metformin can form a complex with zinc ions, increasing zinc bioavailability, and that the metformin-zinc complex may slow viral mul..
Mar 30 2024	Qiu et al., Global Epidemiology, doi:10.1016/j.gloepi.2024.100142	Estimating the effect of realistic improvements of metformin adherence on COVID-19 mortality using targeted machine learning
	Retrospective 61,180 COVID-19 positive patients with chronic metformin prescriptions showing lower COVID-19 mortality with improved metformin adherence, as measured by proportion of days covered.
Mar 27 2024	Dimnjaković et al., PLOS ONE, doi:10.1371/journal.pone.0301056	Association of anti-diabetic drugs and covid-19 outcomes in patients with diabetes mellitus type 2 and chronic kidney disease: Nationwide registry analysis
	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..
Mar 24 2024	Silverii et al., Journal of Clinical Medicine, doi:10.3390/jcm13071874	Is Metformin Use Associated with a More Favorable COVID-19 Course in People with Diabetes?
	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 7 2024	Lewandowski et al., Biomedicines, doi:10.3390/biomedicines12030605	Insulin and Metformin Administration: Unravelling the Multifaceted Association with Mortality across Various Clinical Settings Considering Type 2 Diabetes Mellitus and COVID-19
	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..
Feb 13 2024	De Jesús-González et al., Microorganisms, doi:10.3390/microorganisms12020383	A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin
	Review of the therapeutic potential of metformin and atorvastatin against COVID-19. Authors discuss the immunomodulatory and antiviral capabilities of these commonly prescribed diabetes and cholesterol medications. They note metformin's a..
Feb 11 2024	Petakh et al., Viruses, doi:10.3390/v16020281	Metformin Alters mRNA Expression of FOXP3, RORC, and TBX21 and Modulates Gut Microbiota in COVID-19 Patients with Type 2 Diabetes
	Retrospective 30 COVID-19 patients with type 2 diabetes showing improved T lymphocyte gene expression, gut microbiota diversity, and lower inflammatory markers with metformin treatment. Metformin-treated patients had a 1.96-fold increase ..
Jan 30 2024	Halma et al., Endocrine and Metabolic Science, doi:10.1016/j.endmts.2024.100163	Exploring autophagy in treating SARS-CoV-2 spike protein-related pathology
	Review of autophagy pathways for treating SARS-CoV-2 spike protein-related pathology. Authors note that the spike protein is implicated in long COVID and post-vaccination syndrome through mechanisms like inflammation, vascular damage, and..
Jan 29 2024	Jang et al., Endocrinology and Metabolism, doi:10.3803/EnM.2024.1857	Impact of Antidiabetic Drugs on Clinical Outcomes of COVID-19: A Nationwide Population-Based 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 vent..
Jan 17 2024	Yang et al., Cell Stem Cell, doi:10.1016/j.stem.2023.12.012	SARS-CoV-2 infection causes dopaminergic neuron senescence
	In vitro study suggesting that metformin may protect against SARS-CoV-2-induced neurological disorders. Authors show that SARS-CoV-2 infection induces senescence and inflammation in human pluripotent stem cell-derived midbrain dopamine ne..
Jan 14 2024	Zhang et al., Pathogens, doi:10.3390/pathogens13010075	SARS-CoV-2 ORF3a Protein as a Therapeutic Target against COVID-19 and Long-Term Post-Infection Effects
	Review of the ORF3a protein of SARS-CoV-2 as a therapeutic target for COVID-19 due to its role in viral pathogenesis, triggering cytokine storms, tissue damage, and disease severity. Existing drugs doxycycline, metformin, and ibrutinib ar..
Dec 18 2023	Mehrizi et al., Frontiers in Public Health, doi:10.3389/fpubh.2023.1280434	Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data
	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..
Dec 1 2023	Al-kuraishy et al., European Review for Medical and Pharmacological Sciences, doi:10.26355/eurrev_202312_34583	The potential therapeutic effect of metformin in type 2 diabetic patients with severe COVID-19
	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 mortalit..
Nov 30 2023	Mamari et al., Research Journal of Pharmacy and Technology, doi:10.52711/0974-360X.2023.00831	The effect of Chronic treatments of Type 2-diabetes mellitus on COVID-19 Morbidity and Symptoms Severity
	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 17 2023	Miguel et al., Redox Biology, doi:10.1016/j.redox.2023.102957	Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney
	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 ..
Nov 13 2023	Gomaa et al., Inflammopharmacology, doi:10.1007/s10787-023-01383-x	Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy
	Review of 58 studies with 14,071,273 patients showing a beneficial effect of vitamin D supplementation in COVID-19 and long COVID. 49 studies (86%) with 14,029,411 patients (99.7%) found vitamin D effective, including 12 meta-analyses. Ob..
Nov 7 2023	Avula et al., Journal of Clinical and Translational Science, doi:10.1017/cts.2023.668	Strategies used for the COVID-OUT decentralized trial of outpatient treatment of SARS-CoV-2
	Report on the operation of the COVID-OUT trial noting several issues affecting the reliability of the results: - Use of home pulse oximeters for measuring oxygen saturation: authors note that the FDA warned about inaccuracies with home pu..
Oct 19 2023	Bidari et al., Cureus, doi:10.7759/cureus.47354	Development of a Scoring Method Based on a Chest CT Scan to Determine the Outcomes of COVID-19 Patients
	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 10 2023	Petakh et al., Frontiers in Molecular Biosciences, doi:10.3389/fmolb.2023.1260633	Unveiling the potential pleiotropic effects of metformin in treating COVID-19: a comprehensive review
	Review of the potential pleiotropic effects of metformin in treating COVID-19. Authors explore the potential of metformin, a medication commonly used for type 2 diabetes, as an antiviral and anti-inflammatory agent in COVID-19. Metformin ..
Sep 28 2023	Wang et al., Frontiers in Pharmacology, doi:10.3389/fphar.2023.1215307	Effects of metformin on acute respiratory distress syndrome in preclinical studies: a systematic review and meta-analysis
	Systematic review and meta-analysis of 15 non-COVID-19 preclinical studies of metformin for acute respiratory distress syndrome (ARDS) or acute lung injury (ALI), showing that metformin inhibits pulmonary inflammation and oxidative stress..
Sep 28 2023	Lee et al., Heliyon, doi:10.1016/j.heliyon.2023.e20284	Metformin reduces the risk of developing influenza A virus related cardiovascular disease
	Retrospective clinical study, in vitro study, and mouse study of metformin for influenza A virus (IAV) infection. Authors performed a retrospective analysis of 654 diabetic patients, finding that metformin treatment was associated with a ..
Sep 20 2023	Farah et al., Journal of International Medical Research, doi:10.1177/03000605231198413	Prevalence and risk factors of COVID-19 infection, mortality, and post-infection lung fibrosis in patients with type 2 diabetes: a cross-sectional 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 10 2023	Zihono et al., Folia Medica Indonesiana, doi:10.20473/fmi.v59i3.46944	Metformin Effectiveness in Reducing Mortality among Covid-19 Patients with Type 2 Diabetes Mellitus at a Tertiary Hospital in Indonesia
	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.
Aug 30 2023	Petrelli et al., Acta Biomedica Atenei Parmensis, doi:10.23750/abm.v94iS3.14405	Metformin and Covid-19: a systematic review of systematic reviews with meta-analysis
	31% lower mortality (p<0.0001) and 20% lower severe cases (p=0.03). Systematic review and meta analysis of 36 studies showing significantly lower COVID-19 mortality and severity with metformin use.
Aug 24 2023	Guo et al., Diabetes, Metabolic Syndrome and Obesity, doi:10.2147/DMSO.S417925	Effects of Metformin on COVID-19 Patients with Type 2 Diabetes: A Retrospective 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 18 2023	Greco et al., Biomedicines, doi:10.3390/biomedicines11082292	The Impact of GLP-1 RAs and DPP-4is on Hospitalisation and Mortality in the COVID-19 Era: A Two-Year Observational 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 v..
Aug 12 2023	Zhou et al., Frontiers in Endocrinology, doi:10.3389/fendo.2023.1237832	Clinical characteristics and acute complication of COVID-19 patients with diabetes: a multicenter, retrospective study in Southern China
	Retrospective 298 hospitalized type 2 diabetes patients in China showing metformin use associated with not having COVID-19, however the analysis considers treatment during hospitalization, and authors note that in this population metformi..
Aug 1 2023	Tseng, K., 內科學誌, doi:10.6314/JIMT.202308_34(4).04	Metformin and Coronavirus Disease 2019: A New Deal for an Old Drug
	Review of metformin for COVID-19, particularly in patients with preexisting type 2 diabetes. Author summarizes the evidence that metformin has broad anti-inflammatory, immunomodulatory, antiviral, and endothelial protective effects, in ad..
Jul 13 2023	Taher et al., Experimental and Therapeutic Medicine, doi:10.3892/etm.2023.12114	Anti‑inflammatory effect of metformin against an experimental model of LPS‑induced cytokine storm
	Mouse study showing that metformin attenuated LPS-induced increases in inflammatory cytokines, demonstrating an anti-inflammatory effect that may be useful against cytokine storm. 60 female mice were pretreated with oral or intraperitonea..
Jun 24 2023	Piarulli et al., Nutrition, Metabolism and Cardiovascular Diseases, doi:10.1016/j.numecd.2023.06.016	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?
	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 8 2023	Obiri-Yeboah et al., Endocrine Practice, doi:10.1016/j.eprac.2023.06.001	Association of metformin, dipeptidyl dipeptidase-4 inhibitors, and insulin with COVID-19-related hospital outcomes in patients with type 2 diabetes
	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 no..
Jun 6 2023	Alieva et al., Obesity and metabolism, doi:10.14341/omet12801	Factors influencing the severity of COVID-19 course for patients with diabetes mellitus in tashkent: a retrospective cohort 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.
May 27 2023	Akinosoglou et al., Microorganisms, doi:10.3390/microorganisms11061416	COVID-19 Outcomes and Diabetes Mellitus: A Comprehensive Multicenter Prospective Cohort 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 us..
May 19 2023	Araldi et al., medRxiv, doi:10.1101/2023.05.19.23290214	Effects of antidiabetic drugs on mortality risks in individuals with type 2 diabetes: A prospective cohort study of UK Biobank participants
	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 19 2023	Schlesinger et al., Diabetologia, doi:10.1007/s00125-023-05928-1	Risk phenotypes of diabetes and association with COVID-19 severity and death: an update of a living systematic review and meta-analysis
	31% lower mortality (p<0.0001) and 22% lower severe cases (p<0.0001). Systematic review and meta analysis showing significantly lower COVID-19 mortality and severity with metformin use. Authors analyze 169 studies of diabetes patients, with 23 reporting mortality results and 34 reporting severity results fo..
May 15 2023	Petakh et al., Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2023.114892	The F/B ratio as a biomarker for inflammation in COVID-19 and T2D: Impact of metformin
	Analysis of 115 pateints in Ukraine, providing evidence that the gut microbiome may play a role in the inflammatory response of COVID-19 patients, that the firmicutes/bacteroidetes ratio may be a potential biomarker for inflammation, and ..
May 6 2023	Yen et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2023.110692	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
	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...
Apr 28 2023	Petakh et al., Preprints, doi:10.20944/preprints202304.1127.v1	Metformin Therapy Changes Gut Microbiota Alpha-Diversity in COVID-19 Patients with Type 2 Diabetes: The Role of SARS-CoV-2 Variants and Antibiotic Treatment
	Retrospective 120 hospitalized COVID-19 patients showing lower alpha diversity of gut microbiota associated with antibiotic use, type 2 diabetes, longer hospital stays, higher CRP levels, and higher NLR. Metformin therapy was associated w..
Mar 31 2023	Sandhu et al., PLOS ONE, doi:10.1371/journal.pone.0282961	Outpatient medications associated with protection from COVID-19 hospitalization
	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.
Feb 23 2023	Ma et al., PLOS ONE, doi:10.1371/journal.pone.0282210	Is metformin use associated with low mortality in patients with type 2 diabetes mellitus hospitalized for COVID-19? a multivariable and propensity score-adjusted meta-analysis
	Meta analysis of 22 metformin studies, showing significantly lower mortality with metformin use prior to hospitalization.
Jan 31 2023	Parveen et al., Annals of the National Academy of Medical Sciences (India), doi:10.1055/s-0042-1760353	Association of Metformin with Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis
	37% lower mortality (p<0.0001). Systematic review and meta analysis showing significantly lower mortality with metformin.
Jan 23 2023	Nassar et al., Journal of Diabetes, doi:10.1111/1753-0407.13359	Noninsulin‐based antihyperglycemic medications in patients with diabetes and COVID‐19: A systematic review and meta‐analysis
	40% lower mortality (p<0.0001) and 4% improvement (p=0.86). Meta analysis of 26 studies showing lower mortality with metformin and glucagon-like peptide-1 receptor agonists (GLP-1RA), higher hospitalization and ICU admission with dipeptidyl peptidase-4 inhibitors (DPP-4i), and lower hospitalizatio..
Jan 20 2023	Chertok Shacham et al., Medicine, doi:10.1097/md.0000000000032650	Blood glucose control with different treatment regimens in type 2 diabetes patients hospitalized with COVID-19 infection: A retrospective study
	45% lower mortality (p=0.0001) and 7% shorter hospitalization (p=0.5). Retrospective 359 COVID-19 patients with diabetes in Israel, showing lower mortality in the other treatments group compared to the insulin group, with 80% of the other treatments group receiving metformin. Groups refer to use during hospi..
Jan 6 2023	Pinchera et al., Microorganisms, doi:10.3390/microorganisms11010145	Diabetes and SARS-CoV-2 Infection: The Potential Role of Antidiabetic Therapy in the Evolution of COVID-19
	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.
Dec 31 2022	Khafri et al., Current Research in Medical Sciences, doi:10.22088/crms.6.2.32	Comparison of clinical and laboratory parameters of COVID-19 in diabetic patients using different glucose-lowering drugs: a retrospective study
	Retrospective 157 diabetic patients in Iran reporting shorter hospitalization with metformin, however numbers in this paper are inconsistent. The counts and percentages for death in Table 1 are not possible - 11 (13.92%) for metformin cou..
Dec 24 2022	Bramante et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(23)00299-2	Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial
	41% lower PASC (p=0.01). Long-term 10 month followup for NCT04510194, showing significantly lower incidence of PASC with metformin treatment. Adjusted results are provided for metformin but not for ivermectin or fluvoxamine. For many issues with this trial, see [..
Dec 7 2022	Servais et al., Annals of Endocrinology, doi:10.1016/j.ando.2023.08.002	Mortality-related risk factors of inpatients with diabetes and COVID-19: a multicenter retrospective study in Belgium
	49% lower mortality (p=0.002). Retrospective 375 hospitalized diabetes patients in Belgium, showing lower risk of COVID-19 mortality with metformin use.
Nov 9 2022	Miao et al., Frontiers in Endocrinology, doi:10.3389/fendo.2022.1002834	Metformin use and mortality and length of stay among hospitalized patients with type 2 diabetes and COVID-19: A multiracial, multiethnic, urban observational 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 9 2022	Milosavljevic et al., Journal of Community Hospital Internal Medicine Perspectives, doi:10.55729/2000-9666.1127	Evaluation of Glycemic Control and Predictors of Severe Illness and Death in Patients With Diabetes Hospitalized With COVID-19
	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.
Oct 31 2022	Mannucci et al., Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, doi:10.2147/DMSO.S385646	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
	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 29 2022	Zhan et al., Annals of Pharmacotherapy, doi:10.1177/10600280221133577	Effect of Antidiabetic Therapy on Clinical Outcomes of COVID-19 Patients With Type 2 Diabetes: A Systematic Review and Meta-Analysis
	34% lower mortality (p<0.0001), 65% lower ventilation (p=0.57), and 1% lower ICU admission (p=0.92). Meta analysis of 54 studies (34 for metformin) with a total of over 314,000 patients showing lower mortality with metformin, SGLT-2 inhibitors, and GLP-1 receptor agonists in COVID-19 patients with type 2 diabetes. Metformin, SGLT-2i, and..
Oct 10 2022	Morrison et al., PLOS ONE, doi:10.1371/journal.pone.0275787	COVID-19 outcomes in patients taking cardioprotective medications
	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 4 2022	Ouchi et al., Primary Care Diabetes, doi:10.1016/j.pcd.2022.10.001	Antidiabetic treatment and COVID-19 Outcomes: A population-based cohort study in primary health care in Catalonia during the first wave of the pandemic
	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-metfo..
Oct 1 2022	Petakh et al., Medical Archives, doi:10.5455/medarh.2022.76.329-332	Effects of Metformin, Insulin on Hematological Parameters of COVID-19 Patients with Type 2 Diabetes
	Analysis of hematologic parameters in COVID-19 patients with diabetes in Ukraine, showing significantly lower CRP for patients taking metformin.
Sep 21 2022	Yip et al., SSRN Electronic Journal, doi:10.2139/ssrn.4225660	Metformin Does Not Reduce Hospitalisation for COVID-19
	7% lower combined mortality/hospitalization (p=0.61) and 15% lower progression (p=0.16). Retrospective 12,331 diabetes patients in Hong Kong, showing no significant difference in outcomes with metformin use.
Sep 13 2022	Zaccardi et al., Diabetes, Obesity and Metabolism, doi:10.1111/dom.14872	Ethnicity and risks of severe COVID-19 outcomes associated with glucose-lowering medications: A cohort 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.
Aug 31 2022	Ventura-López et al., Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2022.113223	Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial
	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 a..
Aug 30 2022	Chan et al., medRxiv, doi:10.1101/2022.08.29.22279355	Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes
	59% lower mortality (p=0.66), 54% lower severe cases (p=0.37), and 42% lower progression (p=0.37). Retrospective 3,136 patients with prediabetes and 282 with PCOS, showing metformin associated with reduced COVID-19 severity.
Aug 18 2022	Bramante et al., NEJM, doi:10.1056/NEJMoa2201662	Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19
	52% lower combined mortality/hospitalization (p=0.09), 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 treatm..
Aug 16 2022	Loucera et al., Virology Journal, doi:10.1186/s12985-023-02195-9 (date from preprint)	Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
	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 ..
Aug 9 2022	Shestakova et al., Frontiers in Endocrinology, doi:10.3389/fendo.2022.909874	Risk factors for COVID-19 case fatality rate in people with type 1 and type 2 diabetes mellitus: A nationwide retrospective cohort study of 235,248 patients in the Russian Federation
	22% lower mortality (p=0.001). Retrospective 224,190 type 2 diabetes patients in Russia, showing lower mortality with metformin use.
Jul 6 2022	Cousins et al., Cell Reports Methods, doi:10.1016/j.crmeth.2023.100503 (date from preprint)	Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19
	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 2 2022	Shaseb et al., Advanced Pharmaceutical Bulletin, doi:10.34172/apb.2023.066	Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19
	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 pat..
Jun 30 2022	Nguyen et al., Metabolism, doi:10.1016/j.metabol.2022.155196	Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis
	46% lower mortality (p<0.0001). Meta analysis of 61 studies showing lower mortality with preadmission metformin (42 studies), GLP-1RA, and SGLT-2i use in COVID-19 patients with diabetes. DPP-4i and insulin use were associated with increased mortality, while sulfonylurea..
Jun 29 2022	Hunt et al., Journal of General Internal Medicine, doi:10.1007/s11606-022-07701-3	Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans
	67% lower mortality (p<0.0001). Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including metformin. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a cont..
Jun 9 2022	Yeh et al., BMJ Open Diabetes Research & Care, doi:10.1136/bmjdrc-2022-002774	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
	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.
May 27 2022	Chen et al., Frontiers in Endocrinology, doi:10.3389/fendo.2022.895458	The Association Between Antidiabetic Agents and Clinical Outcomes of COVID-19 Patients With Diabetes: A Bayesian Network Meta-Analysis
	26% lower mortality (p<0.0001). Meta-analysis of 42 studies (25 for metformin) with 7 antidiabetic agents, showing metformin, DPP4i, SGLT2i, and GLP1RA were associated with lower COVID-19 mortality in patients with diabetes compared to non-users, while insulin was assoc..
Apr 1 2022	Ma et al., Scientific Reports, doi:10.1038/s41598-022-09639-2	Metformin is associated with favorable outcomes in patients with COVID-19 and type 2 diabetes mellitus
	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 29 2022	MacFadden et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofac156	Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
	1% fewer cases (p=0.45). Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of metformin.
Mar 7 2022	Wong et al., Frontiers in Endocrinology, doi:10.3389/fendo.2022.810914	Metformin Use in Relation to Clinical Outcomes and Hyperinflammatory Syndrome Among COVID-19 Patients With Type 2 Diabetes: A Propensity Score Analysis of a Territory-Wide Cohort
	59% lower mortality (p=0.01), 61% improved recovery (p=0.005), 64% 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.
Feb 28 2022	Han et al., Archives of Medical Research, doi:10.1016/j.arcmed.2021.08.002	Association Between Anti-diabetic Agents and Clinical Outcomes of COVID-19 in Patients with Diabetes: A Systematic Review and Meta-Analysis
	27% lower mortality (p=0.001). Meta analysis of 31 studies (23 for metformin) showing metformin was associated with significantly lower mortality and poor composite outcomes in diabetic COVID-19 patients. DPP-4 inhibitors, sulfonylurea/glinides, SGLT-2 inhibitors, and ..
Feb 24 2022	Wong et al., Diabetes Care, doi:10.2337/dc21-2186	Glycemic Control and Clinical Outcomes in U.S. Patients With COVID-19: Data From the National COVID Cohort Collaborative (N3C) Database
	51% lower mortality (p<0.0001), 41% lower ventilation (p<0.0001), and 40% lower hospitalization (p<0.0001). N3C retrospective 39,616 COVID-19 patients with diabetes in the USA, showing lower mortality, ventilation, and hospitalization with metformin use.
Feb 23 2022	Ganesh et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.15258	Does metformin affect outcomes in COVID‐19 patients with new or pre‐existing diabetes mellitus? A systematic review and meta‐analysis
	22% lower mortality (p<0.0001). Meta analysis of 32 cohort studies with 2,916,231 patients showing significantly lower mortality with metformin treatment in COVID-19 patients with diabetes, with an unadjusted odds ratio of 0.61 (95% CI: 0.53-0.71) and an adjusted odds r..
Jan 18 2022	Usman et al., Journal of Thrombosis and Thrombolysis, doi:10.1007/s11239-022-02631-7	Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes
	60% lower mortality (p=0.21), 76% lower ventilation (p=0.05), and 34% shorter hospitalization (p=0.13). Retrospective 75 diabetes patients, 34 on metformin, showing improved clinical outcomes with treatment, without statistical significance.
Jan 17 2022	Fu et al., International Journal of Endocrinology, doi:10.1155/2022/9322332	Prognostic Factors for COVID-19 Hospitalized Patients with Preexisting Type 2 Diabetes
	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 10 2022	Ojeda-Fernández et al., Diabetes, Obesity and Metabolism, doi:10.1111/dom.14648	Metformin use is associated with a decrease in risk of hospitalization and mortality in COVID-19 diabetic patients: a population-based study in Lombardy
	16% lower mortality (p<0.0001), 22% lower ICU admission (p=0.01), and 3% lower hospitalization (p=0.11). Retrospective 31,966 COVID+ patients using anti-hyperglycemic drugs in Italy, showing lower mortality and ICU admission with metformin use.
Dec 31 2021	Wallace et al., BMJ Open, doi:10.1136/bmjopen-2021-050051	Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study
	72% lower mortality (p<0.0001). Retrospective 9,532 hospitalized COVID+ veterans in the USA, showing lower mortality with metformin use. The study provides results for use before, after, and before+after. Before+after should more accurately represent prophylaxis up to C..
Nov 30 2021	Al-Salameh et al., Diabetes & Metabolism, doi:10.1016/j.diabet.2021.101297	The association between metformin treatment and COVID-19 outcomes according to metformin continuation during hospitalisation
	55% lower combined mortality/ICU admission (p=0.04). Retrospective 140 diabetic patients in France, showing lower mortality for patients where metformin use was continued after hospitalization.
Nov 19 2021	Parthasarathy et al., bioRxiv, doi:10.1101/2021.11.18.469078	Metformin Suppresses SARS-CoV-2 in Cell Culture
	In Vitro study showing metformin inhibits SARS-CoV-2 in Caco2 cells. Metformin reduced viral titers by nearly 99%, and by about 90% when cells were treated prior to infection.
Nov 8 2021	Bliden et al., Circulation, 144:A12228	Metformin Use in Patients Hospitalized With COVID-19: Lower Inflammation, Oxidative Stress, and Thrombotic Risk Markers and Better Clinical Outcomes
	60% lower mortality (p=0.21) and 76% lower ventilation (p=0.05). Retrospective 75 diabetes patients, 34 on metformin, showing lower mortality with treatment in unadjusted results with minimal group details.
Oct 30 2021	Ong et al., Journal of the ASEAN Federation of Endocrine Societies, doi:10.15605/jafes.036.02.20	Association Between Metformin Use and Mortality Among Patients with Type 2 Diabetes Mellitus Hospitalized for COVID-19 Infection
	47% lower mortality (p=0.02). Retrospective 355 diabetic hospitalized COVID-19 patients in the Philippines, showing lower mortality with metformin use.
Oct 29 2021	Saygili et al., Irish Journal of Medical Science, doi:10.1007/s11845-021-02823-9	Preadmission usage of metformin and mortality in COVID-19 patients including the post-discharge period
	42% lower mortality (p=0.02). Retrospective 586 diabetic hospitalized COVID-19 patients in Turkey, showing lower mortality with existing metformin use.
Oct 6 2021	Wander et al., Diabetes Care, doi:10.2337/dc21-1351	Prior Glucose-Lowering Medication Use and 30-Day Outcomes Among 64,892 Veterans With Diabetes and COVID-19
	15% lower mortality (p<0.0001), 2% lower ICU admission (p=0.62), and 3% lower hospitalization (p=0.09). Retrospective 64,892 veterans with diabetes in the USA, showing lower mortality with existing metformin use.
Sep 29 2021	Li et al., Endocrinology, Diabetes & Metabolism, doi:10.1002/edm2.301	Inpatient use of metformin and acarbose is associated with reduced mortality of COVID-19 patients with type 2 diabetes mellitus
	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 16 2021	Kan et al., Frontiers in Endocrinology, doi:10.3389/fendo.2021.708494	Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis
	31% lower mortality (p=0.001). Meta analysis of 14 studies showing significantly lower COVID-19 mortality with metformin use.
Sep 9 2021	Ando et al., Scientific Reports, doi:10.1038/s41598-021-96720-x	Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States
	39% lower hospitalization (p=0.04). Retrospective 28,093 COVID+ patients in the USA, showing lower risk of hospitalization with metformin use.
Sep 7 2021	Wang et al., BMJ Open Diabetes Research & Care, doi:10.1136/bmjdrc-2021-002299	Evaluation and management of COVID-19-related severity in people with type 2 diabetes
	12% lower ICU admission (p=0.005). Retrospective 16,504 COVID-19 type 2 diabetes patients, showing lower risk of ICU admission with existing metformin use.
Aug 31 2021	Yang et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2021.108977	The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus
	36% lower mortality (p<0.0001). Meta analysis of 17 studies including 20,719 COVID-19 patients with diabetes, showing lower risk of mortality and severity with metformin.
Aug 31 2021	Reis et al., The Lancet Regional Health - Americas, doi:10.1016/j.lana.2021.100142 (date from preprint)	Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial
	27% lower mortality (p=0.53), 6% lower hospitalization (p=0.88), 14% more combined hospitalization/ER visits (p=0.58), and 31% lower progression (p=0.48). Data for the primary outcome in this trial appears to be impossible [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 ..
Aug 20 2021	Cheng et al., Cell Metabolism, doi:10.1016/j.cmet.2020.08.013	Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes
	65% higher mortality (p=0.25). Retrospective 1,213 hospitalized diabetic COVID-19 patients in China, showing no significant difference in mortality with pre-existing metformin use.
Aug 19 2021	Li et al., Frontiers in Medicine, doi:10.3389/fmed.2021.704666	Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis
	34% lower mortality (p<0.0001). Meta analysis of 19 studies showing metformin use associated with lower COVID-19 mortality and hospitalization.
Aug 9 2021	Poly et al., Journal of Clinical Medicine, doi:10.3390/jcm10163507	Metformin Use Is Associated with Decreased Mortality in COVID-19 Patients with Diabetes: Evidence from Retrospective Studies and Biological Mechanism
	34% lower mortality (p<0.0001). Meta analysis of 16 studies of diabetic patients showing significantly lower COVID-19 mortality with metformin use.
Jul 18 2021	Boye et al., Diabetes Therapy, doi:10.1007/s13300-021-01110-1	Risk Factors Associated with COVID-19 Hospitalization and Mortality: A Large Claims-Based Analysis Among People with Type 2 Diabetes Mellitus in the United States
	10% lower hospitalization (p<0.0001). Retrospective 9531 COVID+ diabetes patients in the USA, showing lower risk of hospitalization with existing biguanides treatment (defined as mainly metformin in the abstract and entirely metformin in the text).
Jul 17 2021	Blanc et al., GeroScience, doi:10.1007/s11357-021-00397-z	Therapeutic prevention of COVID-19 in elderly: a case–control study
	79% lower mortality (p=0.06) and 44% more cases (p=0.12). Retrospective 179 patients in France exposed to COVID-19 showing, without statistical significance, a higher risk of cases, and a lower risk of mortality among cases with existing metformin treatment.
Jul 13 2021	Tamura et al., Diabetology & Metabolic Syndrome, doi:10.1186/s13098-021-00695-8	Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies
	97% lower mortality (p=0.02). Retrospective 188 hospitalized patients in Brazil, showing lower risk of mortality with metformin use. Authors note that, although pre-hospital metformin use improved clinical parameters at admission, continuous use during hospitalization..
May 24 2021	Oscanoa et al., Clinical Diabetology, doi:10.5603/DK.a2021.0035	Metformin therapy and severity and mortality of SARS-CoV-2 infection: a meta-analysis
	44% lower mortality (p<0.0001) and 15% lower severe cases (p=0.08). Meta analysis of 32 studies showing significantly lower COVID-19 mortality with metformin use.
May 5 2021	Ravindra et al., medRxiv, doi:10.1101/2021.04.20.21255792	Retrospective Assessment of Treatments of Hospitalized Covid-19 Patients
	30% lower mortality (p=0.42). Retrospective 1,035 hospitalized patients in India. Of 366 diabetic patients, there was lower mortality for the 53 that were on metformin.
May 1 2021	Sun et al., Journal of the Endocrine Society, doi:10.1210/jendso/bvab048.709	Is Metformin Use Associated With a Decreased Mortality for COVID-19 Diabetic Patients? A Meta-Analysis
	47% lower mortality (p=0.005). Meta analysis of 8 studies with 11,169 participants showing lower mortality with metformin use.
Apr 14 2021	Gálvez-Barrón et al., Gerontology, doi:10.1159/000515159	COVID-19: Clinical Presentation and Prognostic Factors of Severe Disease and Mortality in the Oldest-Old Population: A Cohort 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 6 2021	Alamgir et al., medRxiv, doi:10.1101/2021.03.22.21254110	Drug repositioning candidates identified using in-silico quasi-quantum molecular simulation demonstrate reduced COVID-19 mortality in 1.5M patient records
	27% lower mortality (p<0.0001). In Silico study followed by PSM analysis of the National COVID Cohort Collaborative data in the USA, showing 27% lower mortality with metformin use.
Mar 31 2021	Ghany et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2021.02.022	Metformin is associated with lower hospitalizations, mortality and severe coronavirus infection among elderly medicare minority patients in 8 states in USA
	66% lower mortality (p=0.0002), 29% lower hospitalization (p=0.008), and 68% lower ARDS (p<0.0001). Retrospective 1,139 elderly COVID+ patients in the USA, 392 with pre-existing metformin use, showing significantly lower mortality, hospitalization, and ARDS with treatment.
Mar 31 2021	Jiang et al., Diabetes Research and Clinical Practice, doi:10.1016/j.diabres.2020.108619	Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: A retrospective cohort study
	46% lower mortality (p=0.4) and 80% lower progression (p=0.02). Retrospective 328 COVID-19 patients with type 2 diabetes in China, showing significantly lower risk of ARDS with existing metformin use.
Mar 30 2021	Khunti et al., The Lancet Diabetes & Endocrinology, doi:10.1016/S2213-8587(21)00050-4	Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England
	23% lower mortality (p<0.0001). Retrospective 2,851,465 people with type 2 diabetes in the UK, showing lower mortality with existing metformin use. Results are subject to confounding by indication because metformin is typically used early in the progression of type 2 di..
Mar 30 2021	Holt et al., Thorax, doi:10.1136/thoraxjnl-2021-217487	Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
	27% more cases (p=0.42). Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistica..
Mar 23 2021	Bramante et al., Journal of Medical Virology, doi:10.1002/jmv.26873	Outpatient metformin use is associated with reduced severity of COVID‐19 disease in adults with overweight or obesity
	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.
Feb 17 2021	Wargny et al., Diabetologia, doi:10.1007/s00125-020-05351-w	Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study
	28% lower mortality (p=0.03) and 15% higher hospital discharge (p=0.02). Retrospective 2,796 hospitalized diabetes patients with COVID-19 in France, showing lower mortality with metformin use.
Feb 13 2021	Oh et al., Acta Diabetologica, doi:10.1007/s00592-020-01666-7	Metformin use and risk of COVID-19 among patients with type II diabetes mellitus: an NHIS-COVID-19 database cohort study
	26% higher mortality (p=0.3) and 28% fewer cases (p<0.0001). Retrospective 27,493 type II diabetes patients in the USA, 7,204 on metformin, showing significantly lower COVID-19 cases, but no significant difference in mortality.
Jan 31 2021	Lally et al., Journal of the American Medical Directors Association, doi:10.1016/j.jamda.2020.10.031	Metformin is Associated with Decreased 30-Day Mortality Among Nursing Home Residents Infected with SARS-CoV2
	52% lower mortality (p=0.009). Retrospective 775 nursing home residents in the USA, showing lower mortality with existing metformin use.
Jan 13 2021	Crouse et al., Frontiers in Endocrinology, doi:10.3389/fendo.2020.600439	Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes
	61% lower mortality (p=0.02). Retrospective 219 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment.
Dec 28 2020	Ramos-Rincón et al., Research Square, doi:10.21203/rs.3.rs-133358/v1	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
	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 19 2020	Huh et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2020.12.041	Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
	1% higher progression (p=0.11) and 4% fewer cases (p=0.82). Retrospective database analysis showing no significant differences with pre-existing metformin use.
Dec 10 2020	Lalau et al., Diabetes & Metabolism, doi:10.1016/j.diabet.2020.101216	Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19
	22% lower mortality (p=0.16), 18% lower combined mortality/intubation (p=0.21), and 7% lower ventilation (p=0.72). Retrospective 2,449 hospitalized COVID-19 diabetes patients in France, 1,496 with existing metformin use, showing lower mortality with treatment. Statistical significance was reached in model 1 but not in models 2-4 which also adjust for ..
Dec 4 2020	Sourij et al., Diabetes, Obesity and Metabolism, doi:10.1111/dom.14256	COVID‐19 fatality prediction in people with diabetes and prediabetes using a simple score upon hospital admission
	37% lower mortality (p=0.13). Retrospective 247 hospitalized COVID-19 diabetes patients, showing lower mortality with metformin use in unadjusted results.
Dec 3 2020	Bramante et al., The Lancet Healthy Longevity, doi:10.1016/S2666-7568(20)30033-7	Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis
	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.
Nov 30 2020	Scheen, A., Diabetes & Metabolism, doi:10.1016/j.diabet.2020.07.006	Metformin and COVID-19: From cellular mechanisms to reduced mortality
	25% lower mortality (p<0.0001). Meta analysis of 4 observational studies with a total of 10,508 patients showing 25% lower mortality with metformin treatment in type 2 diabetes patients hospitalized for COVID-19.
Nov 17 2020	Kolin et al., PLOS ONE, doi:10.1371/journal.pone.0241264	Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank
	30% more cases (p=0.08). 397,064 patient UK Biobank retrospective showing higher risk of COVID-19 with metformin use, without statistical significance. Metformin is typically prescribed for diabetes, diabetes patients have significantly higher COVID-19 risk, and ..
Nov 16 2020	Pérez-Belmonte et al., BMC Medicine, doi:10.1186/s12916-020-01832-2	Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study
	10% higher mortality (p=0.48). Retrospective 2,666 type 2 diabetes COVID-19 patients in Spain, showing higher mortality with existing metformin use (not statistically significant).
Nov 11 2020	Lukito et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2020.11.006	The Effect of Metformin Consumption on Mortality in Hospitalized COVID-19 patients: a systematic review and meta-analysis
	36% lower mortality (p=0.03). Meta analysis of 9 studies showing lower mortality with metformin use.
Oct 19 2020	Gao et al., Clinical and Translational Science, doi:10.1111/cts.12897	Risk of Metformin in Patients With Type 2 Diabetes With COVID-19: A Preliminary Retrospective Report
	225% higher progression (p=0.05). Retrospective 110 hospitalized COVID-19 patients with diabetes in China, showing increased risk of severity with metformin.
Oct 13 2020	Goodall et al., Epidemiology and Infection, doi:10.1017/S0950268820002472	Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study
	3% lower mortality (p=0.81). Retrospective 981 hospitalized patients in the UK, showing no significant difference with metformin use.
Oct 6 2020	Mirani et al., Diabetes Care, doi:10.2337/dc20-1340	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
	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 1 2020	Li et al., Endocrine Practice, doi:10.4158/EP-2020-0466	Metformin Use in Diabetes Prior to Hospitalization: Effects on Mortality in Covid-19
	78% lower mortality (p=0.02). Retrospective 131 type II diabetes patients with COVID pneumonia, showing lower mortality with existing metformin use. Acarbose (commonly used in China as an initial therapy for diabetes) did not have a similar association with mortality,..
Sep 30 2020	Kow et al., Journal of Medical Virology, doi:10.1002/jmv.26498	Mortality risk with preadmission metformin use in patients with COVID-19 and diabetes: A meta-analysis
	Meta analysis of 5 studies showing lower mortality with metformin use.
Aug 23 2020	Abu-Jamous et al., medRxiv, doi:10.1101/2020.08.20.20174169	Associations of comorbidities and medications with COVID-19 outcome: A retrospective analysis of real-world evidence data
	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 18 2020	Hariyanto et al., Obesity Medicine, doi:10.1016/j.obmed.2020.100290	Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection
	Meta analysis of 5 studies showing lower mortality with metformin use.
Aug 12 2020	Kim et al., Diabetes & Metabolism Journal, doi:10.4093/dmj.2020.0146	The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea
	64% lower mortality (p=0.1) and 52% lower progression (p=0.13). Retrospective 235 hospitalized diabetes patients in South Korea, showing lower mortality and lower progression to severe disease with metformin.
Jul 31 2020	Chen et al., Diabetes Care, doi:10.2337/dc20-0660	Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication
	33% lower mortality (p=0.46). Retrospective 120 COVID-19 diabetes patients, showing non-statistically significantly lower mortality with existing metformin treatment.
Jul 14 2020	Wang et al., Journal of Hematology & Oncology, doi:10.1186/s13045-020-00934-x	A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward
	58% lower mortality (p=0.43). Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing non-statistically significant lower mortality with metformin treatment.
Jun 23 2020	Choi et al., Journal of Clinical Medicine, doi:10.3390/jcm9061959	Clinical Characteristics and Disease Progression in Early-Stage COVID-19 Patients in South Korea
	120% higher progression (p=0.26). Retrospective 293 patients in South Korea, showing higher risk of progression with metformin use, without statistical significance.
May 29 2020	Cariou et al., Diabetologia, doi:10.1007/s00125-020-05180-x	Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO 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 21 2020	Luo et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.20-0375	Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis
	75% lower mortality (p=0.02). Retrospective 283 COVID-19+ diabetes patients in China, showing lower mortality with existing metformin treatment.

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