Common Medication Found Effective at Reducing Odds of Serious Outcomes for COVID-19 Patients

The trial compared the effects of ivermectin, fluvoxamine, and metformin in a randomized double-blind placebo-controlled trial.

Scientists have found that metformin, a commonly prescribed diabetes drug, reduces the chances of emergency department visits, hospitalization, or death.[{” attribute=””>COVID-19 by over 40 percent; and over 50 percent if prescribed early in onset of symptoms. The study, which was published on August 18 in the New England Journal of Medicine, also found no positive effect from treatment with either ivermectin or low-dose fluvoxamine. The research was led by the University of Minnesota Medical School and School of Public Health.

“We are pleased to contribute to the body of knowledge around COVID-19 therapies in general, with treatments that are widely available,” said Carolyn Bramante, MD, principal investigator of the study. Bramante is an assistant professor of internal medicine and pediatrics at the U of M Medical School. “Our trial suggests that metformin may reduce the likelihood of needing to go to the emergency room or be 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. None of the medications in the trial prevented the primary outcome.

The COVID-OUT trial was the nation’s first to study 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 emergency department visits or hospitalization, as well as Long-COVID.

Dr. Carolyn Bramante of the University of Minnesota answers questions about COVID OUT. credit: University of Minnesota Medical School

The study design was simple and straightforward. Patients were randomly assigned to receive one of three drugs individually, placebo, or a combination of metformin and fluvoxamine or metformin and ivermectin. Although the study was placebo-controlled with exact-matched placebo pills, Dr. Bramante says that 83% of volunteers received the drugs, supported by existing data, because of the six-arm design. Each volunteer received 2 types of pills to hide their healing work for 3 to 14 days of treatment. Each participant tracked their symptoms, and after 14 days, they completed a survey.

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

The study included both those who had been vaccinated against COVID-19 and those who were not. This is the first published trial where the majority of participants were vaccinated.

Clinical trials began in January 2021 after scientists at the U of M Medical School identified through computer modeling and observational studies that outpatient metformin use reduces the likelihood of mortality from COVID-19, or Appears to be hospitalized. Their research, in partnership with UnitedHealth Group, was published in Journal of Medical Virology and in Lancet Healthy Longevity, Test-tube studies also found that metformin inhibited the COVID-19 virus in laboratory settings. These findings, as well as additional prospective studies supporting the use of high-dose fluvoxamine and ivermectin, provided evidence for the addition of combination arms to all three drugs.

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

Reference: Carolyn T. Bramante, MD, MPH, Jared D. Huling, PhD, Christopher J. Tignanelli, MD, John B. “Randomized trial of metformin, ivermectin and fluvoxamine for Covid-19” by Buss, MD. , PhD, David M. Leibovitz, MD, Jacinda M. Niklas, MD, MPH, Kenneth Cohen, MD, Michael A. Puskarich, MD, Hrishikesh K. Bellani, MD, MPH, Jennifer L. Propper, BS, Lian K. Siegel, Ph.D., Nicole R. Kleet, Ph.D., David J. Odde, Ph.D., Darlet G. Luke, PharmD, Blake Anderson, MD, Amy B. Karger, MD, PhD, Nicholas E. Ingraham, MD, Katrina M. Hartmann, BA, Via Rao, MS, Aubrey A. Hagen, BA, Barkha Patel, MS, Sarah L. Feno, MPH, Nandini Avula, BS, Neha V. Reddy, BS, Spencer M. Erickson, BA, Sarah Lindbergh, MPH, Regina Frickton, BA, Samuel Lee, BS, Edin Zaman, MD, Hanna G. Severad, Walker J. Tordson, BA, Matthew F. Pullen, MD, Michelle Biros, MD, Nancy E. Sherwood, Ph.D., Jennifer L. Thompson, MD, David R. Boulware, MD, MPH, and Thomas A. Murray, Ph.D. For the COVID-Out Testing Team, 18 Aug 2022, New England Journal of Medicine,
DOI: 10.1056/NEJMoa2201662

Participating clinical trial sites include M Health Fairview and Hennepin Healthcare in Minneapolis,[{” attribute=””>Northwestern University in Chicago, Olive View – UCLA Education & Research Institute in Los Angeles, Optum in Colorado and Indiana, and University of Colorado Denver. Co-investigators on the study include Jared Huling, PhD; Thomas Murray, PhD; Hrishikesh Belani, MD; Michelle Biros, MD; David Boulware, MD; David Leibovitz, MD; Jacinda Nicklas, MD; David Odde, PhD; Matt Pullen, MD; Mike Puskarich, MD; John Buse, MD, PhD; Jennifer Thompson, MD; and Christopher Tignanelli, MD.

The trial received monetary support from the Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants, and UnitedHealth Group.

In addition, this research was supported by the National Institutes of Health’s National Center for Advancing Translational Sciences, grants UL1TR002494 and KL2TR002492, and the National Institute of Digestive, Diabetes, and Kidney diseases K23 DK124654. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health’s National Center for Advancing Translational Sciences.