Green and blue coronavirus cells under magnification intertwined with DNA cell structure
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Researchers from the University of Minnesota (U OF M) Medical School have found that the diabetes drug metformin lowers the risk of developing long COVID. The results of their study, called COVID-OUT which examined whether early outpatient treatment with metformin, ivermectin, or fluvoxamine could precent long COVID were published in the journal Lancet Infectious Diseases.

“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. “Metformin is an inexpensive, safe and widely available drug, and its use as a preventive measure could have significant public health implications.”

COVID-OUT was a placebo-controlled randomized clinical trial that included more than 1,200 participants between the ages of 30 and 85 who qualified as either overweigh or obese. The participants were randomly chosen to receive either metformin or placebo, while another subset received ivermectin, fluvoxamine or their placebos. More than 1,100 of the participants reported their symptoms for 10 months after their initial COVID-19 diagnosis.

In addition to the patients receiving metformin being 40% less likely to develop long COVID, the study also found that if patients began taking the drug less than four days after their symptoms started, their risk of developing long COVID decreased by 63%. This effect was consistent across the different demographic groups in the study, and also consistent across multiple variants of the virus, including the Omicron variant. PatientS treated with either ivermectin or fluvoxamine showed no reduced risk of developing long COVID.

According to the U of M researchers, metformin’s ability to prevent the development of long COVID was predicted by biophysics-based computer model that simulated the life cycle of SARS-CoV-2 from the infection of healthy cells to the release of progeny virions. Metformin was identified early in the process as the model found that protein synthesis was a good targeting for an antiviral approach.

“The trial is a good example of how engineering tools can be used to predict clinical outcomes,” says David Odde, a co-investigator of the trial and professor in the Department of Biomedical Engineering who led the team that developed the simulator. “By steering research efforts toward more effective interventions and away from less effective ones, the COVID-19 simulator focused clinical trial efforts and ultimately helped add to the body of knowledge around disease treatments.”

The investigators believe that this trial is the first randomized, placebo-controlled Phase III trial to evaluate the effect of outpatient therapeutic interventions to help combat the development of long COVID. It was also one of the few trials that has included treating pregnant women. Metformin is safe, inexpensive, widely available, and has few contraindications or medication interactions.

“This long-term outcome from a randomized trial is high-quality evidence that metformin prevents harm from the SARS-CoV-2 virus,” said Bramante. “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.”

The researchers note that with as many as one-in-ten people experiencing symptoms of long COVID, there is an urgent public need to find ways to implement metformin as treatment to prevent its development.

“Long COVID is an important public health emergency that might have lasting health, mental health, and economic sequelae, particularly in socioeconomically marginalized groups, and metformin is safe and widely available at low cost,” the researchers concluded.

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