People who took metformin for nearly one year after SARS-CoV-2 infection showed a 41% decrease in the incidence of long COVID compared with placebo, finds a new analysis of data.
Results from the ‘Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months’ — or ‘COVID-OUT’ — trial show that, of 1,126 patients with a documented positive SARS-CoV-2 PCR or antigen test within three days before enrolment, the cumulative incidence of long COVID by day 300 of follow-up was 6.3% in those treated with metformin (titrated up to 1,500mg per day) and 10.4% who received placebo.
The study, published in The Lancet Infectious Diseases on 8 June 2023, took place across six sites in the United States, and included adults aged 30 to 85 years (median age 45 years), all of whom were overweight or obese.
The participants skewed female (56% compared with 44% who were male) and were predominantly (83%) white.
The study authors said these data are from the first randomised controlled trial to evaluate the effect of outpatient COVID-19 treatment on the incidence of long COVID and suggested that it may point to metformin having a direct antiviral effect on SARS-CoV-2.
“Metformin was shown to reduce the incidence of long COVID and is safe, inexpensive, widely available, and has few contraindications or medication interactions,” the research paper concluded.
However, experts have urged caution over the findings, as they may not be completely generalisable.
Ewan Pearson, professor of diabetic medicine at the University of Dundee, said: “The number of people developing long COVID was relatively small (n=93) and the study population were largely those with private healthcare and were predominantly white.”
Frances Williams, professor of genomic epidemiology at King’s College London, also commented: “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.
“While metformin has very good safety data, being widely used and safe in pregnancy and renal failure, this is a considerable drug burden in the context of a poorly understood condition.”
Adam Jacobs, senior director of biostatistical science at clinical research organisation Premier Research, said: “The most important weakness is that long COVID was not the primary objective of the trial, it was one of the secondary objectives.”
Jacobs added that a previous paper had failed to show a significant difference from placebo on the primary outcome measure of a composite of hypoxia, emergency department visit, hospitalisation or death at 14 days.