Trial Results Suggest Metformin Is Effective at Reducing Odds of Serious COVID-19 Outcomes


University of Minnesota Medical School Analysis shows comparison with fluvoxamine and ivermectin in a double-blinded, placebo-controlled, randomized study.

Metformin, a commonly prescribed diabetes medication, can lower the odds of death, emergency department (ED) visits, or hospitalizations because of COVID-19 by more than 40% and more than 50%, if prescribed early during the onset of symptoms, according to the results of a study published in the New England Journal of Medicine.

Investigators also found that there were no positive effects from treatment with either ivermectin or low-dose fluvoxamine.

“We are pleased to contribute to the body of knowledge around COVID-19 therapies in general, with treatments that are widely available,” Carolyn Bramante, MD, an assistant professor of internal medicine and pediatrics at the University of Minnesota Medical School, said in a statement. “Our trial suggests that metformin may reduce the likelihood of needing to go to the emergency room or be hospitalized for COVID-19.”.

This was the secondary outcome of the trial, Bramante said.

The primary outcome included whether an individual had low oxygen levels on a home oxygen monitor, but none of the medications in the trial prevented this outcome.

The COVID-OUT trial was the nation’s first study about whether metformin, low-dose fluvoxamine, ivermectin, or their combinations could serve as possible treatments to prevent ED visits, hospitalization, and long-COVID.

Individuals in the study were randomly assigned to receive either 1 of the 3 drugs, a placebo, or a combination of metformin and either fluvoxamine or ivermectin. Each individual received 2 types of pills for 3 to 14 days of treatment. They tracked their symptoms and after 14 days completed a survey.

There were 1323 individuals included in the trial, and their body mass index was at least 25 kg/m2 or greater. To qualify for the study the individuals enrolled within 3 days after receiving a positive COVID-19 test and included women who were pregnant.

The majority of individuals in the study were vaccinated.

“Although we know COVID-19 vaccines are highly effective, we know that some new strains of the virus may evade immunity and vaccines may not be available worldwide. So, we felt we should study safe, available, and inexpensive outpatient treatment options as soon as possible,” Bramante said in the statement.

“Understanding whether outpatient treatments could ensure more people survive the illness if they contract it and have fewer long-term symptoms is an important piece of the pandemic response,” she said.

The trial launched in January 2021 after the investigators used computer modeling and observational studies to identify that outpatient metformin use appeared to decrease death or hospitalization from COVID-19. Test tube study results also showed that metformin inhibited the COVID-19 virus in lab settings. These findings, along with other prospective studies supporting the use of higher dose fluvoxamine and ivermectin, provided the evidence to include all 3 medications as well as the combination arm.

These findings were published in the Journal of Medical Virology and in The Lancet Healthy Longevity.

The in-vitro and observational studies are not conclusive but contribute to the body of evidence, Bramante said.

Investigators also enrolled individuals nationwide through 6 institutions in the United States, including Minneapolis, Minnesota, to complete the study.


COVID OUT clinical trial suggests metformin effective at reducing odds of serious outcomes for COVID-19 patients seeking early treatment. News release. EurekAlert. August 18, 2022. Accessed August 18, 2022.

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