Common, inexpensive diabetes drug could cut long COVID risk, study finds

A well-known, inexpensive diabetes drug appears to cut the risk of developing long COVID, hopeful-but-early new research suggests.

The study, published Thursday in the peer-reviewed journal Lancet Infectious Diseases, found outpatient treatment with the drug metformin — a common treatment for Type 2 diabetes — reduced long COVID incidence among infected patients by 41 per cent.

Roughly six per cent of those taking metformin went on to develop the condition, compared to close to 11 per cent of those in the placebo group. Participants on metformin were also less likely to be hospitalized roughly a month after infection by SARS-CoV-2, the virus that causes COVID-19.

"Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost and safe," wrote the research team. 

Lead author Dr. Carolyn Bramante, a physician-scientist with the University of Minnesota in Minneapolis, told CBC News that the effect was even larger when metformin was given quickly — in less than four days — during someone's infection. She said metformin may be helping patients fight off the virus, or reducing inflammation, though more research is needed to figure out why the drug appears to work.

"Our data don't suggest anything about whether metformin would treat long COVID in someone who already has it," she said, "so that's an important area of research where trials should be done."

Two other drugs, ivermectin and fluvoxamine, were also studied, but neither made a difference on the incidence of long COVID.

'Potentially landmark' findings

The research involved randomized, quadruple-blind trials on roughly 1,400 people at six sites in the U.S., through multiple waves of the pandemic, and looked at both vaccinated and unvaccinated individuals — though only those with first-time infections. 

Outside medical experts say it's one of the more robust studies yet on a potential preventative aimed at long COVID.

"I think it's a significant start to having a better understanding of the role of metformin in reducing the risk of long COVID," said Dr. Isaac Bogoch, an infectious diseases specialist with the University Health Network in Toronto. "There's been hints of data over the last couple of years … this furthers that discussion."

If confirmed, the findings are "profound and potentially landmark on two distinct counts," wrote Dr. Jeremy Faust, from Harvard Medical School, in an accompanying commentary in the Lancet.

The paper offers the "first high-quality evidence" showing incidence of long COVID can be reduced through a medical intervention, he wrote, and offers an important medical contribution regarding the very existence of the condition, since "a treatment can only be effective if there is something to treat."

In a statement, Dr. Frances Williams, professor of genetic epidemiology at King's College London, cautioned there would need to be extensive use of metformin to realize the study's seemingly impressive outcomes.

"In total, 564 people were exposed to the drug metformin to prevent 23 hypothetical cases. This means 24 people would need to take metformin to prevent one case of [long COVID]."

Fatigue, 'brain fog'

Marked by a variety of lingering symptoms such as fatigue, shortness of breath and feelings of 'brain fog', and formally known as post COVID-19 condition, long COVID is thought to be less common by this point in the pandemic, largely thanks to widespread protection from vaccinations.

(The impact of metformin on reducing long COVID incidence in the new Lancet study was seen among the unvaccinated group, with little impact on those who were vaccinated and boosted, as the rate of lingering symptoms among those heavily-protected individuals was already significantly lower.)

But the condition can still be debilitating for some, including millions of people around the world — including many in Canada — who became infected with earlier SARS-CoV-2 variants before the arrival of vaccines. 

While physicians are hopeful the new research may fuel additional study and potentially help bring down long COVID rates even further, there were some key limitations.

For one thing, it only focused on adults between age 30 and 85 who were overweight or had obesity — so the drug's impact on individuals of other body weights isn't yet known.

"It's not entirely clear how generalizable this will be," Bogoch said.

In his comment for the Lancet, Faust also noted that since the participants were given a diabetes drug, there may be reduced symptoms linked to undiagnosed diabetes among the patients. "Furthermore, the mechanism of action by which metformin might reduce the incidence of long COVID remains unclear," he wrote.

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Dr. Lynora Saxinger, a professor in the division of infectious diseases at the University of Alberta, noted the study didn't follow long COVID patients using any "standardized criteria."

But, she said in an email to CBC News, "it still is really positive and encouraging that a treatment in early COVID could reduce risk of prolonged symptoms: additional studies in other patient groups and with more specific long COVID symptom followup will be really helpful."

Nicole Chevrier, a long COVID sufferer who has been coping with lingering symptoms for more than a year, warned using any drug to tackle the complex condition will remain a challenge, given the wide array of health impacts and the challenges people still face in getting a proper diagnosis.

"A one-size fits all drug solution is, at this point, looking very much pie in the sky," she wrote in an email to CBC News.

She added that the nature of how long COVID develops — sometimes becoming apparent weeks or months after an initial infection — "would make it very difficult to pinpoint when a drug should be taken to ward it off [unless] it would be prescribed to everyone who contracted the infection."

Bogoch stressed that, while the drug shows potential, it wouldn't "solve all of our issues with long COVID." However, it could become an important tool given its decades-old safety profile, he said. 

"If this is something that, indeed, pans out, and if metformin truly has some properties that reduce the risk of developing long COVID, that's wonderful because it's a cheap, widely available [drug]."