COVID OUT clinical trial suggests metformin effective at reducing odds of serious outcomes for COVID-19 patients seeking early treatment

Aug. 22, 2022
Trial compared effect of ivermectin, fluvoxamine, and metformin in randomized double-blinded placebo- controlled trial.

Published in the New England Journal of Medicine, researchers — led by the University of Minnesota Medical School and School of Public Health — have found that metformin, a commonly prescribed diabetes medication, lowers the odds of emergency department visits, hospitalizations, or death due to COVID-19 by over 40 percent; and over 50 percent if prescribed early in onset of symptoms. The study also found no positive effect from treatment with either ivermectin or low-dose fluvoxamine.

Carolyn Bramante, MD, principal investigator of the study and an assistant professor of internal medicine and pediatrics at the U of M Medical School 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 medications in the trial prevented the primary outcome.

The COVID-OUT trial studied whether metformin, a medication for type 2 diabetes; low-dose fluvoxamine, an antidepressant; and ivermectin, an antiparasitic, or their combinations 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 the three drugs individually, placebo, or a combination of metformin and fluvoxamine or metformin and ivermectin. Although the study was placebo-controlled with exact-matching placebo pills, Dr. Bramante says 83% of volunteers received medications 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, they completed a survey.

The 1323 participants in the trial were limited to adults with a body mass index greater than or equal to 25 kg/m2, which qualifies as overweight – for instance, 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 after receiving a positive COVID-19 test. It was among the first randomized clinical trials for COVID-19 to include pregnant women.

The study included those who were vaccinated and those who were not. The majority of participants were vaccinated. 

The clinical trial launched in January 2021 after U of M Medical School researchers identified, through computer modeling and observational studies, that outpatient metformin use appeared to decrease the likelihood of mortality from or being hospitalized for COVID-19. Their research, in partnership with UnitedHealth Group, was published in the Journal of Medical Virology and in The Lancet Healthy Longevity. Test-tube studies also found that metformin inhibited the COVID-19 virus in lab settings. These findings, along with additional prospective studies supporting the use of higher-dose fluvoxamine and ivermectin, provided the evidence to include all three medications as well as combination arms.

University of Minnesota release