• Posted June 9, 2023

Diabetes Med Metformin Might Help Prevent Long COVID

A safe, generic diabetes pill can help people avoid long COVID, a new clinical trial shows.

Metformin cut the risk of long COVID by about 40% for patients who received a two-week course of the drug while battling their infection, the researchers reported.

The results were even more dramatic if COVID-19 patients began taking metformin soon after infection. Starting on the drug within three days of symptom onset cut long COVID cases by more than 60% in those folks.

This is the first clinical trial to suggest that any drug taken during COVID-19 infection might reduce the risk of long COVID, the study authors noted.

“This shows that 14 days of metformin treatment, when started early after infection, prevents diagnosis of long COVID over the subsequent 10 months,” said lead researcher Dr. Carolyn Bramante, an assistant professor with the University of Minnesota Medical School, in Minneapolis.

Long-term symptoms associated with a COVID-19 infection are an emerging chronic illness that potentially affects millions of people around the world, the researchers said in background notes.

Long COVID is thought to be caused by the damage that infection inflicts on different organs in the body, such as the brain, lungs or heart. That's why symptoms can vary between patients.

A symptom checklist for long COVID published in May included brain fog, fatigue, post-exertional malaise, dizziness, gastrointestinal problems, heart palpitations, changes in sexual desire or capacity, altered ability to smell or taste, chest pain, chronic cough, thirst and abnormal movements.

Those researchers estimated that about 10% of people infected during the initial Omicron wave developed long COVID within six months of their illness, according to the study in the Journal of the American Medical Association.

Metformin has been approved in the United States since 1995 for the treatment of diabetes, but the drug also had been known to have antiviral properties.

Lab tests have shown that metformin could potentially keep the COVID virus from replicating and spreading, which prompted this clinical trial, Bramante explained.

In the trial, 564 COVID-19 patients were randomly chosen to receive a two-week course of metformin, while another 562 received an inactive placebo pill. Patients were recruited between December 2020 and January 2022.

All patients were overweight or obese based on their body mass index, which is known to be a risk factor for severe COVID infection. They were all 30 or older and suffered mild to moderate infections that did not require hospitalization.

Doctors started the metformin patients on a 500 milligram (mg) dose that was gradually ramped up to 1,500 mg daily by the end of the 14 days. According to Drugs.com, the cost of metformin is around $11 for 14 of the 500 mg tablets.

The researchers then tracked all the patients for 10 months to see who developed long COVID.

A two-week course of metformin reduced the risk of long COVID by 41% overall compared to placebo, and by 63% if patients started the drug early in their infection, the results showed.

The study was published online June 8 in the Lancet Infectious Diseases journal.

The findings reflect previously published results from this trial which found that metformin prevented more than 40% of emergency department visits, hospitalizations and deaths due to COVID-19 within two weeks of starting treatment.

Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases, called the trial results “provocative, interesting and very encouraging.”

“In science, we like to see things confirmed,” Schaffner said, urging further study of metformin. “That said, I think once this information gets out, there are going to be any number of physicians, nevermind patients, who say, ‘Metformin, I know how to use this drug. It's safe. It's effective. And if we can reduce the risk of long COVID, which is in the minds of lots of patients when they get sick, it's worth a try.'”

Bramante said the antiviral activity of metformin likely is the main reason why it appears to prevent long COVID, but that the drug also reduces harmful inflammation caused by infection.

Metformin also is very safe for people to take, particularly if they're just on it for two weeks, Bramante said.

“The way metformin treats diabetes is mostly by reducing inflammation in the liver, and it stops the body from making more glucose,” Bramante said. “Metformin doesn't lower glucose like insulin does, so metformin doesn't cause dangerously low blood sugar in people with or without diabetes.”

Schaffner said metformin could be a welcome addition to current COVID treatments, particularly since nothing had yet been shown to reduce the risk of long COVID.

“At the moment, what we tell everybody to do is get vaccinated. Keep up to date with your vaccinations, because that's the single best thing we can do to not only prevent COVID, but long COVID,” Schaffner said. “But if we add to this the notion that particularly people in high-risk groups who do get infected could take metformin for two weeks and reduce the risk of long COVID, well, that gives us a nice therapeutic option.”

More information

The U.S. Centers for Disease Control and Prevention has more about long COVID.

SOURCES: Carolyn Bramante, MD, MPH, assistant professor, University of Minnesota Medical School, Minneapolis; William Schaffner, MD, medical director, National Foundation for Infectious Diseases; The Lancet, June 8, 2023, online