March 9, 2023 – Metformin appears to play a task in stopping Long COVID when taken early during a COVID-19 infection, based on a new preprint Studying The Lancet. This preprint has not been peer-reviewed or published in a journal.
Specifically, metformin resulted in a 42% reduction in long-COVID cases in individuals with mild to moderate COVID-19 infection.
“Long COVID affects millions of people, and preventing long COVID with a treatment like metformin could prevent significant disruption in people’s lives,” says lead creator Carolyn Bramante, MD, assistant professor of internal medicine and pediatrics on the University of Minnesota.
Between January 2021 and February 2022, Bramante and colleagues tested three oral medications—metformin (normally used to treat type 2 diabetes), ivermectin (an antiparasitic drug), and fluvoxamine (an antidepressant)—in a clinical trial called COVID-OUT within the United States. The subjects, researchers, caregivers, and others involved within the study were unaware of the randomized treatments. The study was decentralized, with no face-to-face contact with participants.
Researchers included patients ages 30 to 85 who were obese or obese, had a confirmed COVID-19 infection, had symptoms for lower than 7 days, had no known previous infection, and entered the study inside 3 days of their positive test. The study included monthly follow-up for 300 days, and participants reported whether or not they had received a long-term diagnosis of COVID from a physician, which researchers confirmed in medical records after participants gave consent.
The medications were prepackaged in pill boxes in order that participants could arrive quickly and take the right variety of each form of pill. The packages were shipped the identical day via courier or overnight.
Metformin doses were divided over 14 days: 500 milligrams on the primary day, 500 milligrams twice day by day for the next 4 days, after which 500 milligrams within the morning and 1,000 milligrams within the evening for the remaining nine days.
Of the 1,323 people studied, 1,125 agreed to take part in a long-term follow-up for long-COVID, including 564 within the metformin group and 561 within the blinded placebo group. The average age was 45 years and 56% were women, including 7% pregnant women.
The average time from symptom onset to starting medication was 5 days, and 47% began taking the drugs inside 4 days or less. About 55% had received the first COVID-19 vaccination series, including 5.1% who had received a primary booster dose before entering the study.
Overall, 8.4% of participants reported that a physician had diagnosed them with long COVID. Of those taking metformin, 6.3% developed long COVID, compared with 10.6% of those taking the similar placebo.
The risk reduction of metformin compared with placebo was 42%, a consistent result across all subgroups, including vaccination status and different COVID-19 variants.
If metformin was began lower than 4 days after the onset of COVID-19 symptoms, the effect was potentially even greater, with a 64% reduction. In comparison, the reduction was 36% for individuals who began taking metformin 4 or more days after the onset of symptoms.
Neither ivermectin nor fluvoxamine showed any profit in stopping long COVID.
At the identical time, the authors of the study warn that further research is required.
“The COVID-OUT trial does not indicate whether metformin would be effective in preventing long COVID if treatment was started at the time of an emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as a treatment in individuals who already have long COVID,” they wrote. “Given the burden that long COVID places on society, confirmation in a trial that takes into account the limitations of our study is urgently needed to translate these findings into practice and policy.”
The evaluation revealed several risk aspects for Long COVID. About 11.1% of ladies had a Long COVID diagnosis, in comparison with 4.9% of men. In addition, those that had received at the very least the first vaccination had a lower risk of developing Long COVID (6.6%), in comparison with 10.5% of the unvaccinated. Only considered one of the 57 individuals who received a booster shot developed Long COVID.
Notably, pregnant and breastfeeding individuals were included on this study, which is vital because pregnant individuals are at higher risk for poor COVID-19 outcomes and are excluded from most non-obstetric clinical trials, the study authors wrote. In this study, they were randomized to receive either metformin or placebo, but not ivermectin or fluvoxamine, because there is restricted research on the protection of those drugs while pregnant and breastfeeding.
The results are currently being reviewed in peer-reviewed journals, but show consistent results from other recent studies. In addition, the authors published Published results from COVID-OUT, which showed that metformin resulted in a 42 percent reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.
“Given the lack of side effects and the high cost of a two-week treatment, I think these data now support the use of metformin,” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD's sister site for healthcare professionals.
Topol, who was not involved on this study, has been a number one voice in COVID-19 research throughout the pandemic. He pointed to the necessity for further studies, including a factorial design study to check metformin and paxlovid, which has shown promise in stopping long COVID. Topol has also wrote about the preprint In Fundamental truthsits online newsletter.
“As I have written in the past, I do not use the term 'breakthrough' lightly,” he wrote. “But given that metformin is so safe and inexpensive and shows such a pronounced benefit in the current randomized trial, I would classify it as a breakthrough.”
In other words, Topol wrote, based on this study, he would take metformin himself if he became infected with COVID-19.
Jeremy Faust, MD, an emergency physician at Brigham and Women's Hospital in Boston, also wrote about the study in his newsletter Internal MedicineHe noted that the 42 percent reduction in Long COVID implies that 23 COVID-19 patients have to be treated with metformin to forestall a Long COVID diagnosis, which represents a “significant reduction.”
“Conclusion: If a one that meets the factors for obesity or obese asked me in the event that they should take metformin (for two weeks) as soon as they discover they've COVID-19, I'd say Yes in lots of, if not most, cases, based on this recent data,” he wrote. “This is beginning to seem like an actual victory.”