March 9, 2023 — Metformin appears to play a role in preventing long COVID when taken early during a COVID-19 infection, according to a new preprint to study from The Lancet. The preprint has not yet been peer reviewed or published in a journal.
In particular, metformin caused a 42% decrease in long COVID in people who had mild to moderate COVID-19 infection.
“Long COVID affects millions of people, and preventing Long COVID with a treatment like metformin could prevent significant disruptions in people’s lives,” says lead author Carolyn Bramante, MD, assistant professor of internal medicine. and Pediatrics at the University of Minnesota.
Between January 2021 and February 2022, Bramante and his colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic) and fluvoxamine (an antidepressant) – in a clinical trial across the United States called COVID-OUT. Study subjects, investigators, healthcare providers, and others involved in the study were not told about the randomized treatments. The trial was decentralized, with no face-to-face contact with participants.
The researchers included patients between the ages of 30 and 85 who were overweight or obese, had evidence of confirmed COVID-19 infection, had less than 7 days of symptoms, had no known prior infections, and joined the study within 3 days of their positive test. . The study included monthly follow-up for 300 days, and participants indicated whether they had received a lengthy diagnosis of COVID from a physician, which researchers confirmed in medical records after participants gave consent.
Medications were prepackaged in pill boxes for quick delivery to participants and to ensure they took the correct number of each type of pill. The parcels were sent by courier the same day or by overnight dispatch.
Metformin doses were distributed over 14 days: with 500 milligrams on the first day, 500 milligrams twice daily for the next 4 days, then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.
Of the 1,323 people studied, 1,125 agreed to long-term follow-up for long COVID, including 564 in the metformin group and 561 in the blinded placebo group. The average age was 45 years and 56% were women, of which 7% were pregnant.
The average time from onset of symptoms to start of treatment was 5 days and 47% started taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who had received an initial booster, before enrolling in the study.
Overall, 8.4% of participants said they had been diagnosed with long COVID by a medical professional. Among those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical placebo.
The risk reduction for metformin was 42% compared to placebo, which was consistent across all subgroups, including vaccination status and different COVID-19 variants.
When metformin was started within 4 days of the onset of COVID-19 symptoms, the effect was potentially even greater, with a 64% reduction, compared to a 36% reduction in those who started metformin. metformin after 4 or more days after symptoms.
Neither ivermectin nor fluvoxamine showed benefit in preventing long COVID.
At the same time, the study authors warn that more research is needed.
“The COVID-OUT trial does not indicate whether or not metformin would be effective in preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as a treatment in people who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses the limitations of our study. to translate these findings into practice and policy.”
Several risk factors for long COVID emerged in the analysis. About 11.1% of women had a long COVID diagnosis, compared to 4.9% of men. Additionally, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, compared to 10.5% among the unvaccinated. Only one of the 57 people who received a booster shot developed long COVID.
Notably, pregnant and breastfeeding women were included in this study, which is important given that pregnant women are at higher risk for poor COVID-19 outcomes and are excluded from most non-obstetric clinical trials, the authors wrote. study authors. In this study, they were randomized to receive metformin or a placebo, but not ivermectin or fluvoxamine due to limited research on the safety of these drugs during pregnancy and lactation.
The results are currently under review, but show consistent results from other recent studies. Also, in August 2022, the authors published results of COVID-OUT which showed that metformin led to a 42% reduction in hospital visits, emergency room visits and deaths related to the severe form of COVID-19.
“Given the lack of side effects and the cost of a 2-week course, I believe these data support the use of metformin now,” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor of Medscape. , WebMD’s sister site for healthcare professionals.
Topol, which was not involved in this study, has been a leading voice in COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which showed promise in preventing long COVID. Topol too wrote on preprint In Basic Truthsits online newsletter.
“As I have written in the past, I do not use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of it being so safe and inexpensive, I would give it a breakthrough categorization.”
Another way to put it, Topol wrote, is that based on this study, he would take metformin himself if he were infected with COVID-19.
Jeremy Faust, MD, an emergency physician at Brigham and Women’s Hospital in Boston, also written on the study in its newsletter, Inside medicine. He noted that the 42% reduction in long COVID means 23 COVID-19 patients need to be treated with metformin to avoid a long COVID diagnosis, which is a “significant reduction.”
“Conclusion: If someone who meets the criteria for obesity or overweight asked me if they should take metformin (for 2 weeks) as soon as they find out they have COVID-19, I would say Yes in many cases, if not most, based on this new data,” he wrote. “It’s starting to look like a real win.”