Metformin therapy significantly lowers incidence of long Covid

A randomized phase 3 study from the Cold Spring Harbor Laboratory found that the incidence of Long Covid was 42% lower in the metformin group than in the blinded control group.

Long Covid is a new chronic condition that might impact millions of people and occasionally make it impossible for them to work or engage in regular daily activities. This research, COVID-OUT, was a phase 3, quadruple-blinded, placebo-controlled, investigator-initiated, randomized, multi-site clinical investigation. To effectively share placebo controls, the design evaluated three oral medications (metformin, fluvoxamine, and ivermectin) at the same time. Long Covid outcomes were monitored for 10 months to determine whether early outpatient treatment of SARS-CoV-2 with ivermectin, metformin, or fluvoxamine prevents Long Covid.

In the US, 1,125 persons aged 30 to 85 who were overweight or obese, had less than seven days' worth of symptoms, and had signed up within three days of having a confirmed SARS-CoV-2 infection participated in this decentralized, remotely administered experiment. Fluvoxamine, 50 mg on day one and 50 mg twice a day for 14 days. Immediate release metformin, titrated over 6 days to 1,500 mg per day for a total of 14 days. A predetermined secondary objective was the participant reporting a medical provider's diagnosis of Long Covid by day 300 following randomization; the trial's primary outcome was severe Covid by day 14.

The key findings of this study were:

1.45 years old on average, 56% female, and 7% pregnant. Native Americans made up 2% of the population, followed by Asians at 3.7%, Black/African Americans at 7.4%, Whites at 82.8%, and Hispanics at 12.7%.

2.The average BMI was 29.8 kg/m2, and 51% had a BMI more than 30 kg/m2.

3.Overall, 6.3% of those on metformin and 10.6% of those taking a metformin control, 8.0% of those taking ivermectin and 8.1% of those taking a fluvoxamine control, and 10.1% of those taking a fluvoxamine control reported receiving a diagnosis of Long Covid from a medical professional.

4.The Hazard Ratio (HR) for Long Covid was 0.58 for the metformin group, 0.99 for the ivermectin group, and 1.36 for the fluvoxamine group when compared to the control group.

Reference:

Bramante, C. T., Buse, J. B., Liebovitz, D., Nicklas, J., Puskarich, M. A., Cohen, K., Belani, H., Anderson, B., Huling, J. D., Tignanelli, C., Thompson, J., Lindberg, S., Wirtz, E. L., … Boulware, D. R. (2022). Outpatient treatment of Covid-19 with metformin, ivermectin, and fluvoxamine and the development of Long Covid over 10-month follow-up. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.12.21.22283753