Study Shows Metformin Lowers Long COVID Risk

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06/13/2023

John Buse, MD, PhD, co-authored a study showing that the common diabetes drug metformin substantially decreased the risk of developing long COVID after infection from SARS-CoV-2. The clinical trial was led by researchers at the University of Minnesota.


John Buse, MD, PhD

In a new study published in The Lancet Infectious Diseases, University of Minnesota researchers and colleagues found that metformin, a drug commonly used to treat diabetes, prevents the development of long COVID.

The study, called COVID-OUT, investigated if early outpatient COVID-19 treatment with metformin, ivermectin or fluvoxamine could prevent long COVID. Long COVID is a chronic illness that can affect up to 10% of people who have had COVID-19.

“The results of this study are important because long COVID can have a significant impact on people’s lives,” said Carolyn Bramante, MD, principal investigator and an assistant professor at the University of Minnesota Medical School. “Metformin is an inexpensive, safe and widely available drug, and its use as a preventive measure could have significant public health implications.”

This was a large, placebo-controlled randomized clinical trial which enrolled volunteers across the United States. The study found:

  • Those who received metformin were more than 40% less likely to develop long COVID than those who received an identical looking placebo.
  • For participants who started metformin less than four days after their COVID symptoms started, metformin decreased the risk of long COVID by 63%.
  • The effect was consistent across different demographic populations of volunteers who participated and across multiple viral variants, including the Omicron variant.
  • Ivermectin and fluvoxamine did not prevent long COVID.

“Not only did we demonstrate that metformin, an inexpensive and safe treatment, may prevent the development of long COVID in many people, but we validated that long COVID is a real disease in that a 14-day treatment can reduce the risk of long COVID symptoms and a doctor’s diagnosis over many months,” said UNC site PI John Buse, MD, PhD, the Verne S. Caviness Distinguished Professor of Medicine and senior associate dean for clinical research at the UNC School of Medicine.

Buse, who co-led the conception, design and oversight of the study, is the director of the NC Translational and Clinical Sciences (NC TraCS) Institute. The UNC School of Medicine was not a site for the clinical trial.

The study included more than 1,200 participants who were randomly chosen to receive either metformin or placebo, and an additional subset received ivermectin, fluvoxamine or their placebos. Participants were between 30 and 85 years old who qualified as overweight or obese. Over 1,100 of the participants reported on their symptoms for up to 10 months after their initial COVID-19 diagnosis.

“This long-term outcome from a randomized trial is high-quality evidence that metformin prevents harm from the SARS-CoV-2 virus,” said Dr. Bramante, who is also an internist and pediatrician with M Health Fairview. “While half of our trial had been vaccinated, none had been previously infected with the COVID-19 virus. Further research could show whether it is also effective in those with previous infection or in adults with lower body mass index.”

Metformin’s ability to stop the virus was predicted by a simulator developed by U of M Medical School and College of Science and Engineering Biomedical Engineering faculty. The model has been highly accurate to date, successfully predicting, among others, the failure of hydroxychloroquine and the success of remdesivir before the results of clinical trials testing these therapies were announced.

Funding was provided by the Parsemus Foundation, Rainwater Charitable Foundation, Fast Grants and the United Health Foundation. This research was also supported by the National Institutes of Health’s National Center for Advancing Translational Sciences under award number [UL1TR002494, KL2TR002492, and UM1TR004406].

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