Trial suggests metformin effective in reducing risk of severe outcomes for COVID-19 patients seeking early treatment

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

“We are pleased to contribute to the body of knowledge about 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 of M’s medical school. “Our trial suggests that metformin may reduce the likelihood of having to go to the emergency room or be hospitalized with COVID-19.”

Bramante noted that this was a secondary result 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 drug for type 2 diabetes; low-dose fluvoxamine, an antidepressant; and ivermectin, an antiparasitic, or combinations thereof could serve as possible treatments to prevent ER visits or hospitalization, as well as Long-COVID.

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

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

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

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

The clinical trial was launched in January 2021 after researchers at the U of M School of Medicine identified, through computer modeling and observational studies, that outpatient metformin use appeared to reduce the likelihood of death or hospitalization for COVID-19. Their research, in partnership with UnitedHealth Group, has been published in the Journal of Medical Virology and in The Lancet Healthy longevity. Test-tube studies have also found that metformin inhibits the COVID-19 virus in the lab. These results, along with other prospective studies supporting the use of higher doses of fluvoxamine and ivermectin, provided evidence for including all three drugs as well as the combination arms.

“Observational studies and in vitro experiments cannot be conclusive but contribute to the accumulation of evidence,” said Bramante, who is also an internist and pediatrician at M Health Fairview. “To carry out this study, we recruited volunteers nationwide through six institutions in the United States, including Minneapolis.”