Other substances

Metformin

An antidiabetic.

Phase of research

Potential treatment - clinical evidence

How it helps

Other treatment

Drug status

Used to treat other disease

Supporting references

Contradictory references

AI-suggested references

Clinical trials

General information

Metformin is a biguanide antidiabetic. It has antihyperglycemic properties and reduces LDL cholesterol and triglyceride levels (NCIt).

The TOGETHER trial data show that metformin does not reduce the rate of COVID-19-related hospitalization among high-risk patients. No other clinical benefit was observed either (Reis et al., 2022).

Metformin on PubChem
Metformin on DrugBank
Metformin on Wikipedia

Marketed as

ACTOPLUS MET; AVANDAMET; FORTAMET; GLUBRAVA; GLUCOPHAGE; GLUCOVANCE; GLUMETZA; GLYCON; INVOKAMET; JANUMET; JENTADUETO; KAZANO; KOMBIGLYZE; KOMBOGLYZE; QTERNMET; RIOMET; SEGLUROMET; SYNJARDY; TRIJARDY; VELMETIA; XIGDUO

CN(C)C(=N)N=C(N)N

Supporting references

Link	Tested on	Impact factor	Notes	Publication date
Observational Study of Metformin and Risk of Mortality in Patients Hospitalized with Covid-19 Preprint	Patients		significantly associated with reduced mortality in women with obesity or type 2 diabetes hospitalized with COVID-19	Jun/20/2020
A SARS-CoV-2 protein interaction map reveals targets for drug repurposing Small molecule	in silico	42.78		Apr/30/2020
The association between metformin treatment and COVID-19 outcomes according to metformin continuation during hospitalisation Small molecule In vitro	Diabetic patients		The use of metformin in diabetic patients hospitalized with COVID-19 has been linked to improved outcomes. It is unclear whether this positive correlation is due to metformin treatment given before hospitalization, continued use during hospitalization, or both. Sample size: 140.	Oct/23/2021
Metformin in acute respiratory distress syndrome: An opinion ARDS Small molecule In vitro	Bovine pulmonary artery endothelial cells (BPAEC)		Metformin at moderate doses improves the integrity of the vascular barrier by boosting the transendothelial resistance of endothelial cell layers.	Dec/10/2020
Metformin suppresses SARS-CoV-2 in cell culture Small molecule In vitro	Calu3 (HTB-55™; ATCC), Vero (CCL-81™; ATCC) and Caco2 (HTB-37™; ATCC) cells		In cell culture models, the growth of SARS-CoV-2 is notably suppressed by metformin.	Nov/20/2022
Metformin is associated with reduced COVID-19 severity in patients with prediabetes Severe severity Small molecule Moderate severity Mild severity Cohort study	Patients with prediabetes or with polycystic ovary syndrome		In cell culture models, the growth of SARS-CoV-2 is notably suppressed by metformin. Patients who have prediabetes or PCOS (polycystic ovary syndrome) and use metformin appear to experience less severe COVID-19. Sample size: Prediabetes: 400 (Metformin) + 2736 (levothyroxine/control), PCOS: 196 (metformin) + 86 (levothyroxine/control). Main outcome: COVID-19 clinical severity.	Nov/14/2022
Metformin Use in Diabetes Prior to Hospitalization: Effects on Mortality in Covid-19 Small molecule Cohort study	Diabetes patients		Metformin has the potential to be effective in patients who have both COVID-19 and type 2 diabetes mellitus. Sample size: 37. Main outcome: Hospitalization and mortality with a diagnosis of COVID-19 until the 60th day.	Oct/01/2020
Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes Small molecule Cohort study	Diabetes patients		The use of metformin before a diagnosis of COVID-19 has been linked to a significant and strong reduction in mortality among individuals with diabetes. Sample size: 604.	Jan/13/2021
Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis Small molecule Cohort study	Patients with diabetes or obesity		Metformin reduced the mortality rate among women who were hospitalized with COVID-19. However, there was no significant reduction in mortality among men. Sample size: 2333 + 3923 control. Main outcome: The hospital mortality rate determined using the hospital disposition indicator.	Dec/03/2020
Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis Severe severity Small molecule Critical severity Moderate severity Mild severity Cohort study	Diabetic patients		The use of metformin to treat diabetes seems to be linked to a reduction in mortality among patients who have contracted COVID-19. Sample size: 104 + 179 control.	May/21/2020
Metformin is associated with favorable outcomes in patients with COVID-19 and type 2 diabetes mellitus Small molecule Cohort study	Patients with pre-existing type 2 diabetes mellitus		Patients with both COVID-19 and type 2 diabetes mellitus who were treated with metformin prior to hospitalization may have a higher chance of survival. Sample size: 361 + 995 control. Main outcome: Hospitalization or in-hospital mortality.	Apr/01/2022
Effects of Metformin, Insulin on Hematological Parameters of COVID-19 Patients with Type 2 Diabetes Small molecule Cohort study	Patients with Type 2 Diabetes Mellitus		COVID-19 patients with type 2 diabetes who used metformin before being admitted to the hospital experienced a decrease in their CRP (C-reactive protein) levels. Sample size: 25 + 35 control. Dosage: 1 g per day (metformin) or 35 unit per day (insulin).	Oct/01/2022
Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19 Small molecule Cohort study	Diabetes patients		The utilization of metformin may be connected to a lower probability of death among patients with diabetes who were hospitalized for COVID-19. Sample size: 1496 + 953 control. Main outcome: A combination of tracheal intubation for mechanical ventilation and death occurring within seven days of admission.	Dec/10/2020
Preadmission usage of metformin and mortality in COVID-19 patients including the post-discharge period Cohort study Small molekule	Diabetes patients		Using metformin before being admitted to the hospital is linked to a decrease in the likelihood of dying from any cause after being hospitalized for COVID-19. Sample size: 120 + 120 control. Main outcome: Death from all causes within at least 90 days.	Oct/29/2021

AI-suggested references

Link	Publication date
Cationic Compounds with SARS-CoV-2 Antiviral Activity and Their Interaction with Organic Cation Transporter/Multidrug and Toxin Extruder Secretory Transporters.	Jul/11/2021
Metformin use is associated with a decrease in risk of hospitalization and mortality in COVID-19 diabetic patients: a population-based study in Lombardy.	Jan/25/2022
SARS-CoV-2 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1.	Jan/08/2022
A new application of mTOR inhibitor drugs as potential therapeutic agents for COVID-19.	Jul/02/2021
Repurposing metformin for covid-19 complications in patients with type 2 diabetes and insulin resistance.	May/31/2021
Metformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation.	Jun/10/2021
The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus.	Jul/22/2021
Outpatient metformin use is associated with reduced severity of COVID-19 disease in adults with overweight or obesity	Mar/23/2021
Metformin is Associated with Decreased 30-Day Mortality Among Nursing Home Residents Infected with SARS-CoV2.	Oct/26/2020
Treatment with a DPP-4 inhibitor at time of hospital admission for COVID-19 is not associated with improved clinical outcomes: data from the COVID-PREDICT cohort study in The Netherlands.	Jun/26/2021
Therapeutic Potential of Metformin in COVID-19: Reasoning for Its Protective Role.	Mar/14/2021
Uncovering antiobesity-related hypertension targets and mechanisms of metformin, an antidiabetic medication	Mar/08/2021
A proposed mechanism for the possible therapeutic potential of Metformin in COVID-19	Mar/03/2021
Inpatient use of metformin and acarbose is associated with reduced mortality of COVID-19 patients with type 2 diabetes mellitus	Oct/09/2021
Effects of metformin, insulin on COVID-19 patients with pre-existed type 2 diabetes: A multicentral retrospective study.	Mar/19/2021
Metformin Use Is Associated with Decreased Mortality in COVID-19 Patients with Diabetes: Evidence from Retrospective Studies and Biological Mechanism.	Aug/09/2021
Association of metformin with susceptibility to COVID-19 in people with Type 2 diabetes	Jan/22/2021
Exploring Drugs and Vaccines Associated with Altered Risks and Severity of COVID-19: A UK Biobank Cohort Study of All ATC Level-4 Drug Categories Reveals Repositioning Opportunities.	Sep/18/2021
Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: a retrospective cohort study	Oct/06/2020
Metformin is associated with lower hospitalizations, mortality and severe coronavirus infection among elderly medicare minority patients in 8 states in USA	Feb/18/2021
Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes	Jan/18/2022
Liraglutide Improved Cardiometabolic Parameters More in Obese than in Non-obese Patients with Type 2 Diabetes: A Real-World 18-Month Prospective Study	Nov/30/2021
Metformin Suppresses Monocyte Immunometabolic Activation by SARS-CoV-2 Spike Protein Subunit 1	Dec/14/2021
Diabetes and coronavirus (SARS-CoV-2): Molecular mechanism of Metformin intervention and the scientific basis of drug repurposing	May/24/2020
CoMET: a randomised controlled trial of co-commencement of metformin versus placebo as an adjunctive treatment to attenuate weight gain in patients with schizophrenia newly commenced on clozapine	Oct/16/2021
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	Jun/30/2021
Risk of metformin in type 2 diabetes patients with COVID-19: a preliminary retrospective report	Oct/19/2020
Metformin use is associated with reduced mortality rate from coronavirus disease 2019 (COVID-19) infection.	Aug/18/2020
Expression of the SARS-CoV-2 receptorACE2 in human heart is associated with uncontrolled diabetes, obesity, and activation of the renin angiotensin system	Dec/15/2020
Ex vivo SARS-CoV-2 infection of human lung reveals heterogeneous host defense and therapeutic responses	Sep/22/2021
Immunomodulatory and Antiviral Activity of Metformin and Its Potential Implications in Treating Coronavirus Disease 2019 and Lung Injury.	Aug/18/2020
ACE2, Metformin, and COVID-19	Jul/31/2020

Clinical trials

ID	Title	Status	Phase	Start date	Completion date
NCT04604678	Pilot Study Into the Use of Metformin and LDN for Patients With COVID-19	Not yet recruiting	Phase 2	Feb/01/2021	Oct/01/2021
Alternative id - ALRx003 Interventions - Drug: Metformin\|Drug: Naltrexone Study type - Interventional Study results - No Results Available Locations - AgelessRx, Ann Arbor, Michigan, United States Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: None (Open Label)\|Primary Purpose: Treatment Enrollment - 80 Age - 30 Years to 70 Years (Adult, Older Adult) Outcome measures - Reduction of COVID-19 symptoms after 1 week of treatment with metformin and LDN\|Reduction of COVID-19 symptoms after 2 weeks of treatment with metformin and LDN\|Reduction in recovery time from COVID-19\|Reduction in hospitalizations\|Reduction in requirement of additional treatment due to COVID-19\|Reduction in mortality
NCT04510194	COVID-OUT: Early Outpatient Treatment for SARS-CoV-2 Infection (COVID-19)	Active, not recruiting	Phase 3	Jan/01/2021	Feb/01/2023
Alternative id - GIM-2020-29324 Interventions - Drug: Metformin\|Drug: Placebo\|Drug: Fluvoxamine\|Drug: Ivermectin Study type - Interventional Study results - No Results Available Locations - Olive View UCLA Medical Center, Sylmar, California, United States\|University of Colorado Denver; Department of Medicine; Anschutz Health and Wellness Center, Aurora, Colorado, United States\|New West Physicians, Golden, Colorado, United States\|Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States\|American Health Network of Indiana, Greenfield, Indiana, United States\|Hennepin County Medical Center, Minneapolis, Minnesota, United States\|University of Minnesota, Minneapolis, Minnesota, United States Study designs - Allocation: Randomized\|Intervention Model: Factorial Assignment\|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)\|Primary Purpose: Treatment Enrollment - 1350 Age - 30 Years to 85 Years (Adult, Older Adult) Outcome measures - Clinical Progression\|Maximum symptom severity\|Clinical Progression Scale\|Time to meaningful recovery\|Laboratory Outcome Subsidy - Viral Load\|Laboratory Outcome Subsidy\|Laboratory Outcome Subsidy - Microbiome\|Portion of participants with Post-Acute Sequelae of SARS-CoV-2 infection (PASC)
NCT04625985	Metformin Glycinate, Treatment of Patients With COVID-19 and Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2.	Completed	Phase 2	Jul/14/2020	Mar/18/2021
Alternative id - SIL-30000-II-20(2) Interventions - Drug: Metformin Glycinate\|Drug: Placebo oral tablet Study type - Interventional Study results - No Results Available Locations - The American British Cowdray Medical Center, I.A.P, Mexico City, Mexico Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)\|Primary Purpose: Treatment Enrollment - 20 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Viral load\|consciousness level\|temperature\|systolic blood pressure\|Oxigen saturation\|Heart rate\|respiratory rate\|Days of hospitalization\|Days of supplementary oxygen if applies\|Days of supplementary mechanical ventilation\|Toxicity of study drug assessed by incidence of adverse events (grade 3 or 4)\|Changes in laboratory test results
NCT04626089	Metformin Glycinate in Patients With MS or DM2 , Hospitalized With COVID-19 and SARS Secondary to SARS-CoV-2	Withdrawn	Phase 2	Feb/01/2021	Feb/01/2021
Alternative id - SIL-30000-II(1) Interventions - Drug: metformin glycinate\|Drug: Placebo oral tablet Study type - Interventional Study results - No Results Available Locations - Hospital Juárez de México, OPD, Mexico City, Mexico Study designs - Allocation: Randomized\|Intervention Model: Parallel Assignment\|Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)\|Primary Purpose: Treatment Enrollment - 0 Age - 18 Years and older (Adult, Older Adult) Outcome measures - Viral Load\|Days of supplementary oxygen if apply\|Days of supplementary mechanical ventilation if apply\|Days of Hospitalization\|Normalization of fever\|Normalization of oxigen saturation\|Number of deaths\|Change in Serum creatinine levels\|Change in serum Troponin I\|Change in serum aspartate aminotransferase levels\|Change in serum Creatine kinase-MB levels\|Incidence of adverse event

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