Study: Diabetes Drug Metformin May Help Prevent Long COVID

Fact checked by Nick Blackmer

• Metformin, a low-cost, widely-used diabetes drug, may help some people avoid developing long COVID.

• New research, published in The Lancet Infectious Diseases, found that people with overweight or obesity who took metformin after testing positive for COVID were 41% less likely to develop long COVID in the following 10 months.

• Though more research is needed, it’s possible that metformin could be included in long COVID prevention strategies in the future.

The diabetes drug metformin may help prevent people who have overweight or obesity from developing long COVID, a new study found.

Metformin is a low-cost and widely-used drug used to treat type 2 diabetes. But in recent years, researchers have found that metformin has an even broader range of benefits, including limiting cancer, cardiovascular disease, and now it seems, long COVID.

The research, published in The Lancet Infectious Diseases on June 8, found that people who took metformin after testing positive for COVID were 41% less likely to develop long COVID in the 10 months after their infection, compared to a placebo group.

Some study participants also took fluvoxamine and ivermectin—which has been inaccurately touted as a COVID cure—alongside metformin or on their own. The study found that these medications had “no effect” on long COVID incidence.

“Those of us who do diabetes and obesity research had seen, over the last decade or two, articles coming out periodically about how metformin inhibited other viruses in test tubes,” Carolyn Bramante, MD, MPH, principal investigator of the trial and assistant professor of medicine at the University of Minnesota Medical School, told Health. “It made sense that metformin could also inhibit SARS-COV-2.”

Experts are still learning more about long COVID, but the Centers for Disease Control and Prevention describe it as a collection of respiratory, neurological, digestive, or other symptoms that can last for weeks, months, or years after a COVID infection. Recent estimates say that about 10% of people who’ve been infected with the virus develop long COVID.

Here’s what experts had to say about the study’s results, why metformin may be effective against COVID, and how it may impact future treatment of long COVID.

Metformin Shown to Reduce Risk of Developing Long COVID

Dr. Bramante and her team wanted to see how common medications might affect COVID outcomes for people at risk of developing severe symptoms.

The trial included 1,323 participants aged 30 to 85 classified as having obesity or being overweight based on their body mass index (BMI). All had tested positive for COVID in the previous three days and had symptoms for less than seven days.

Researchers randomly assigned the participants to take, for two weeks, either a placebo, metformin plus fluvoxamine or ivermectin, or just metformin, ivermectin, or fluvoxamine.

The researchers initially examined how each medication combination affected participants’ risk of severe COVID by day 14. That research, published last summer, found that none of the three medications prevented low oxygen levels, emergency visits, hospitalization, or death due to COVID. However, patients who took metformin were much less likely to experience these outcomes than people given fluvoxamine or ivermectin.

In light of these results, the researchers kept up with 1,126 participants and documented how many developed long COVID in the 10 months following their infection. About 6.3% of people who took metformin ended up with long COVID, compared to 10.4% of those who took a placebo.

What is BMI?

Body Mass Index, or BMI, is a biased and outdated metric that uses your weight and height to make assumptions about body fat, and by extension, your health. This metric is flawed in many ways and does not factor in your body composition, ethnicity, sex, race, and age. Despite its flaws, the medical community still uses BMI because it’s an inexpensive and quick way to analyze health data.

The risk of developing long COVID was even lower for people who started taking metformin within three days of developing symptoms. That group saw an over 60% reduction in long COVID risk, compared to the 41% reduction for those who took metformin after having symptoms for an extended period of time, Dr. Bramante said.

“We should never over-interpret subgroups like that, but that is biologically consistent with trials that show that the antiviral medications work the sooner you start them,” she explained.

According to Dr. Bramante, researchers included participants with higher BMIs in the study because they have a higher chance of severe COVID outcomes and developing long COVID.

People who have overweight or obesity are also more likely to have inflammation in their body, she explained. Metformin is considered anti-inflammatory, so its protective effects may have been clearer in people with higher BMIs.

It’s possible that the findings could apply to people who do not have overweight or obesity, Dr. Bramante said. However, that has yet to be confirmed.

“This study doesn’t address use in patients at lower risk for acute COVID complications,” David Liebovitz, MD, study co-author and co-director of the Institute for Augmented Intelligence Medicine at the Northwestern University Feinberg School of Medicine, told Health in a statement.

“The finding here was that treating patients during the acute infection who were at elevated risk for COVID-19 complications, ultimately also translated into reduced risk for long COVID,” he said.

Related: Long COVID Symptoms May Include Hair Loss and Sexual Dysfunction, Study Shows

Why Would a Diabetes Drug Affect COVID Outcomes?

It may seem odd that a type 2 diabetes drug could reduce the risk of severe COVID complications and long COVID, but metformin has properties that may equip it to help.

“For typical use, metformin reduces glucose production in the liver,” Dr. Liebovitz said. “This has beneficial effects on patients with diabetes or at risk for diabetes. While we do not know the precise mechanism against developing long COVID, there are a few possibilities based on other evidence.”

Early in 2020, researchers looked into proteins vital to the virus’ life cycle, and identified one called mTOR, Dr. Bramante said. Metformin is one medication that restricts mTOR in the body, making it almost like an antiviral drug.

If long COVID is related to parts of the virus lingering in the body—as some researchers believe—this explains why metformin may prevent the condition from developing.

Metformin can also “reduce oxidative stress on cells and reduce inflammation,” Dr. Liebovitz added. Though it’s unclear if inflammation directly causes long COVID, one study in hamsters found a link between long COVID symptoms and inflammation. Taking metformin, therefore, could reduce the risk of symptoms.

Related: How Long COVID May Be Affecting Your Workouts—And What to Do About It

What Does This Mean for Long COVID Treatment?

As promising as the research results seem, there are still many unanswered questions.

In addition to not knowing whether the results would extend to people with lower BMIs, researchers also don’t know if metformin could have the same impact on people younger than 30 or those who take it for longer than two weeks. It’s also unknown whether people who already have long COVID would benefit from the drug, or if the results might change now that such a large majority of Americans have been vaccinated or previously infected.

“A little bit over half of the sample [group] was vaccinated,” Dr. Bramante said. “That is some evidence of including people with some degree of immunity, but we did not enroll individuals who had a known prior infection. And so that’s an open question.”

Despite the limitations of the trial, it’s possible that metformin could be included in long COVID prevention strategies going forward.

It’s always best to replicate study results before they become widely adapted into medical practice, Dr. Bramante said, but guidelines were loosened during the pandemic so that providers could try new therapies or treatments, even without years of testing.

Metformin has a lot going for it—most importantly, it is very safe and has few side effects, Dr. Bramante said. It’s also relatively inexpensive—30 tablets of 500 milligrams (mg) of metformin, the dosage used in the study, costs about $13.

“Doctors may see our results and choose to prescribe metformin to their patients. It’s an existing medication, so that is an option to them,” Dr. Bramante said.

Still, Dr. Liebovitz added, metformin is “not yet listed as a treatment on the CDC website for acute COVID-19 treatment.” More research may be necessary.

For more Health news, make sure to sign up for our newsletter!

Read the original article on Health.