Metformin shown to reduce incidence of long-COVID

Metformin cuts the risk of developing long COVID by 41%, opening the door to a treatment for a condition that many practitioners find baffling. Long COVID can be anything from a single symptom to something that includes serious multi-organ involvement. And severity can range anywhere from being mild and short-lived, to chronically debilitating. A randomized trial in the Lancet showed metformin was associated with lower long-COVID incidence over placebo and other treatments. The primary outcome of the (COVID-OUT) study was severe COVID-19 by day 14 after starting the study drug. But a key secondary outcome, reported in this study, was the incidence of long COVID. Studies had already shown that metformin inhibits SARS-CoV-2 and prevents severe COVID-19, making it a compelling treatment to study. The randomized, quadruple-blind, placebo-controlled, phase 3 trial was conducted at six sites in the U.S.. A total of 1,126 adults aged 30 to 85 years who had COVID-19 symptoms for fewer than seven days, along with a confirmed COVID-19 test, were included. Also, to be included in the study participants were overweight or obese (defined as BMI ≥25 kg/m² or ≥23 kg/m² for people who were Asian or Latino). They had no known previous SARS-CoV-2 infections. “Women who were pregnant or lactating were not excluded, which is noteworthy given that pregnant women with COVID-19 are at risk of poor outcomes and are excluded from 99% of non-obstetric clinical trials . . . there is a large body of literature to support the safety of metformin during pregnancy and lactation,” the study said. Of the 632 women in the study, 44 were pregnant. Overall, participants had an average age of 45 years, 43.9% were male, and the median BMI was 29.8 kg/m² with 548 (48.7%) having a BMI of greater than 30 kg/m². The trial assessed three oral medications: metformin, ivermectin and fluvoxamine against placebo and analyses were done in three separate randomized comparisons. Participants were randomly assigned to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. The median duration from symptom onset to study drug initiation was five days, the study said. The active followup period for the trial was 28 days. After that, starting 60 days after randomization, surveys asking about health were sent every 30 days up to 10 months. A total of 564 the patients received metformin for 14 days and 562 received matched placebo; 361 received ivermectin and 378 received matched placebo, and 297 received fluvoxamine and 298 received matched placebo. Overall, 93 (8.3%) of the participants developed a long COVID diagnosis by the end of the study period (10 months). The researchers reported that the cumulative incidence of long COVID by day 300 was 6.3% in participants who received metformin and 10.4% among in those who were in the matched placebo group. The effect of metformin was consistent between all the subgroups. Importantly, the earlier metformin had been initiated in patients the stronger the protective effect against developing long-COVID. Neither ivermectin nor fluvoxamine had an impact. “Treatment with metformin during acute COVID-19 infection reduced the risk of long COVID by day 300 by 41.3% compared with placebo,” the study said. The findings “are profound and potentially landmark,” said Dr. Jeremy Faust, emergency physician and instructor at Harvard Medical School, in an accompanying editorial in the journal. “To our knowledge, this is the first high-quality evidence from a randomized controlled trial to show that the incidence of long COVID can be reduced by a medical intervention.” But the editorial also implied that the study helps confirm the reality of long COVID by reducing the incidence of medical issues post-COVID infection. “We cannot modify diseases that do not exist,” he wrote. Dr. Faust added that it is not known how metformin might help, but it “could be that metformin modifies autoimmune cascades triggered by host responses to infection.” On Twitter, Canada’s Dr. Isaac Bogoch said of the study: "Metformin is cheap, safe & widely available. A really well-run clinical trial.” He is an associate professor of medicine at the University of Toronto.

Metformin shown to reduce incidence of long-COVID

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