Metformin reduces SARS-CoV-2 viral load, study finds
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Key takeaways:
- SARS-CoV-2 viral loads among people who received metformin were 4.4 times lower compared with people who received placebo.
- The diabetes drug was also associated with a lower risk for developing long COVID.
SEATTLE —SARS-CoV-2 viral loads were more than four times lower among participants in a phase 3 trial who received the diabetes drug metformin than among those who received placebo, according to findings presented at a medical conference.
The data were from a secondary analysis of the COVID-OUT trial, which evaluated the effectiveness of three repurposed drugs — metformin, ivermectin and fluvoxamine — for the treatment of COVID-19 among patients with overweight or obesity.
Of the three drugs, only metformin showed “a possible benefit for the prevention” of severe COVID-19 that would need to be confirmed in additional studies, according to the researchers. Those results, initially published in The New England Journal of Medicine in August 2022, showed that the diabetes drug reduced the risk for ED visit, hospitalization or death by 42%.
“Looking at metformin, it has an interesting history,” Carolyn Bramante, MD, MPH, an assistant professor of medicine at the University of Minnesota Medical School, said last month during a presentation at the Conference on Retroviruses and Opportunistic Infections.
“Some of the first papers published about it were about influenza and less severe outcomes in influenza,” Bramante said. “It has [also] been studied recently in infectious disease trials and in vitro assays against other RNA viruses like Zika, suggesting an effect against RNA viruses.”
She noted another research group at the University of California, San Francisco, that published a paper showing metformin limited viral growth, and suggested biotranslation was key to disrupting SARS-CoV-2’s viral life cycle. Additionally, she said that observational trials of the drug suggested clinical trials were warranted.
Bramante and colleagues enrolled 1,323 adults aged 30 to 85 years starting on Jan. 1, 2021, within 3 days of lab-confirmed SARS-CoV-2 infection and less than 7 days after symptom onset.
After randomly assigning participants to receive either metformin (1,000 mg/day on days 2 to 5 of treatment and 1,500 mg/day on days 6 to 14), ivermectin, fluvoxamine and/or exact/matching placebo, the researchers mailed medications to each of the participants, along with nasal swabs to be sent back in provided preaddressed mailers. The subset of COVID-OUT participants who sent back swabs are the basis of the secondary analysis.
According to the researchers, 945, 871 and 775 participants collected and returned nasal swabs on days 1, 5 and 10, respectively.
Metformin’s antiviral effect increased with increased dosing during days 6 to 14, and a larger antiviral effect was seen among unvaccinated participants compared with vaccinated participants, the researchers reported.
According to the results, the mean decrease in viral load from baseline to follow-up among participants treated with metformin was 4.4-fold greater vs. placebo.
The researchers observed no change in viral load vs. placebo among participants receiving either ivermectin or fluvoxamine. They concluded that metformin was effective, although the results suggested a dose-dependent effect.
“Metformin showed prevention of severe COVID-19, prevention of long COVID and an antiviral effect — and this is all consistent with other data,” Bramante said. “Metformin is very safe, has very few contraindications, and next steps could be to consider looking at it in combination therapy [for COVID-19].”
References:
- Bramante C, et al. Abstract 170. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 19-22, 2023; Seattle.
- Bramante C, et al. medRxiv 2022;doi:10.1101/2022.12.21.22283753.
- Bramante C, et al. N Engl J Med. 2022;doi:10.1056/NEJMoa2201662.
- COVID-OUT: Early outpatient treatment for SARS-CoV-2 infection (COVID-19). https://clinicaltrials.gov/ct2/show/NCT04510194. Accessed March 30, 2023.
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Bramante C, et al. Abstract 170. Presented at: Conference on Retroviruses and Opportunistic Infections; Feb. 19-22, 2023; Seattle.
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