The widely prescribed diabetes drug, metformin, appears to be valuable in fighting COVID-19, according to a study that found metformin can decrease the amount of COVID-19 virus in the body and also lower the chances of the virus coming back strongly after initial treatment.

Writing in Clinical Infectious Diseases, University of Minnesota (U of M) Medical School–led researchers pointed out that a higher viral load usually indicates a greater concentration of the virus. That often can be an indicator of infection severity.

“The results of the study are important because COVID-19 continues to cause illness, both during acute infection and for months after infection,” said Carolyn Bramante, MD, principal investigator and assistant professor at the U of M Medical School.

The study team advised that metformin has antiviral activity against RNA viruses, including SARS-CoV-2. The antiviral activity apparently occurs because of suppression of protein translation via targeting the host mechanistic target of rapamycin pathway.

“In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58% of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%,” the researchers reported.

COVID-OUT was a 2x3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin. For the study, 945 participants self-collected anterior nasal swabs on Day 1, 871 on Day 5, and 775 on Day 10. The researchers then quantified viral load using reverse-transcription quantitative polymerase chain reaction.

The results indicated that the mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (–0.56log10 copies/mL; 95% CI, –1.05 to –.06; P = .027). “Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI, .55 to .94),” according to the study team. “Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI, .36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo.”

The report concluded that the randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2 found that metformin significantly reduced SARS-CoV-2 viral load and the action might “plain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology.”

The research team suggested that metformin treatment for adults recently infected with COVID-19 could reduce the amount of the virus in the nose and keep the amount of virus from becoming elevated again.

“Among the volunteers in this randomized trial, there was a more than 41% reduction of long COVID among those receiving metformin and a 58% reduction in hospitalization by 28 days. This new study explains why this occurred. Metformin reduced the amount of SARS-CoV-2 virus present, which likely accounts for why this $1 medication reduced hospitalizations and long COVID,” said David Boulware, MD, MPH, an infectious disease physician and professor at the U of M Medical School.

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