The University of Minnesota researchers discovered that metformin, a medicine typically used to treat diabetes, reduces the development of protracted COVID in a recent study published in The Lancet Infectious Diseases.

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 U of M Medical School, adding, "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 randomised 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.

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 and qualified as overweight or obese. Over 1,100 of the participants reported their symptoms for up to 10 months after their initial COVID-19 diagnosis.

"This long-term outcome from a randomised trial is high-quality evidence that metformin prevents harm from the SARS-CoV-2 virus," said Dr. Bramante, who is also an internist and paediatrician with M Health Fairview, adding, "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 the 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.