Trial suggests metformin is effective in reducing odds of serious outcomes for COVID-19 patients seeking early treatment

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In a work published in New England Journal of Medicine, researchers, led by the University of Minnesota School of Medicine and School of Public Health, have found that metformin, a commonly prescribed diabetes drug, reduces the odds of emergency department visits, hospitalizations or death from COVID-19 in more than 40 percent, and more than 50 percent if prescribed early in the onset of symptoms. The study also found no positive effect of treatment with low-dose ivermectin or fluvoxamine.

“We are pleased to contribute to the body of knowledge around COVID-19 therapies in general, with treatments widely available,” said Carolyn Bramante, MD, the study’s principal investigator and assistant professor of internal medicine and pediatrics at the U. from the School of Medicine M. “Our trial suggests that metformin may reduce the likelihood of needing to go to the emergency room or being hospitalized for COVID-19.”

Bramante noted that this was a secondary outcome of the trial; the primary outcome included whether someone had low oxygen on a home oxygen monitor, and none of the trial drugs prevented the primary outcome.

The COVID-OUT trial was the first in the country to study whether metformin, a type 2 diabetes medication; low-dose fluvoxamine, an antidepressant; and ivermectin, an antiparasitic, or their combinations could serve as potential treatments to prevent emergency room visits or hospitalization, as well as Long-COVID.

The study design was simple: patients were randomly assigned to receive one of the three drugs individually, placebo, or a combination of metformin and fluvoxamine or metformin and ivermectin. Although the study was placebo-controlled with exactly-matched placebo pills, Dr. Bramante says 83 percent of volunteers received medication supported by existing data because of the six-arm design. Each participant received 2 types of pills to keep their treatment assignment masked, for 3 to 14 days of treatment. Each volunteer tracked their symptoms and, after 14 days, completed a survey.

Dr. Carolyn Bramante of the University of Minnesota answers questions about COVID OUT. Credit: University of Minnesota School of Medicine

The 1,323 trial participants were limited to adults with a body mass index greater than or equal to 25 kg/m2, which qualifies as overweight, for example, someone who was at least five feet six inches tall and weighed more than 155 pounds. To be eligible for the study, volunteers enrolled within three days of receiving a positive COVID-19 test. It was one of the first randomized clinical trials of COVID-19 to include pregnant women.

The study included those who were vaccinated and those who were not. This is the first published trial where the majority of participants were vaccinated.

“Although we know that vaccines against COVID-19 are very effective, we know that some new strains of the virus can evade immunity, and vaccines may not be available worldwide. So we thought we should explore safe, available and affordable outpatient treatment options as soon as possible,” said Bramante. “Understanding whether outpatient treatments could ensure that more people survive the disease if they contract it and have fewer long-term symptoms is an important part of the response to the pandemic.”

The clinical trial was launched in January 2021 after University of Medicine researchers identified, using computer models and observational studies, that outpatient use of metformin appeared to decrease the likelihood of death from COVID-19 or being hospitalized. Their research, in collaboration with UnitedHealth Group, was published in the Journal of medical virology yen The Lancet Healthy Longevity. Test tube studies also found that metformin inhibited the COVID-19 virus in laboratory settings. These findings, along with additional prospective studies supporting the use of higher doses of fluvoxamine and ivermectin, provided the evidence to include all three medications as well as combination arms.

“Observational studies and in vitro experiments may not be conclusive, but they do contribute to bodies of evidence,” said Bramante, who is also an internist and pediatrician at M Health Fairview. “To complete this study, we enrolled volunteers across the country across six US institutions, including Minneapolis.”

Study finds no benefit to taking ivermectin for symptoms of COVID-19

More information:
Carolyn T. Bramante et al, Randomized trial of metformin, ivermectin, and fluvoxamine for Covid-19, New England Journal of Medicine (2022). DOI: 10.1056/NEJMoa2201662

Carolyn T. Bramante et al, Outpatient metformin use is associated with reduced severity of COVID-19 disease in overweight or obese adults, Journal of medical virology (2021). DOI: 10.1002/jmv.26873

Carolyn T Bramante et al, Metformin and risk of mortality in hospitalized patients with COVID-19: a retrospective cohort analysis, The Lancet Healthy Longevity (2020). DOI: 10.1016/S2666-7568(20)30033-7

Provided by the University of Minnesota Medical School

Summons: Trial suggests metformin is effective in reducing odds of serious outcomes for early treatment-seeking COVID-19 patients (2022, August 18) Retrieved August 20, 2022, from https://

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