Daily Dose: Metformin Reduces Risk of Long COVID

Patient Care brings primary care clinicians a lot of medical news every day—it’s easy to miss an important study. The Daily Dose provides a concise summary of one of the website's leading stories you may not have seen.

On June 12, 2023, we reported on a study published in The Lancet Infectious Diseases that examined whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine could reduce the risk of long COVID in adults with overweight or obesity.

The study

Researchers conducted a decentralized, quadruple-blind, parallel-group phase 3 study across 6 US sites. Adults aged 30-85 years with overweight or obesity who had COVID-19 symptoms for less than 7 days and a documented SARS-CoV-2 positive PCR antigen test within 3 days before enrollment were included in the study.

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 findings

Between December 30, 2020, and January 28, 2022, investigators assessed 6602 persons for eligibility, of whom 1431 were enrolled. Among 1323 participants in the primary, modified intention-to-treat population, 1126 consented for long-term follow-up and completed at least 1 survey after the assessment for long COVID at day 180 (564 received metformin and 562 received matched placebo). Overall, 1074 (95%) of 1126 adults (median age, 45 years; 43.9% women) finished at least 9 months of follow-up or reported a long COVID diagnosis.

Investigators observed that among the 1126 participants who consented for long-term follow-up, 93 (8.3%) reported a receipt of long COVID diagnosis by day 300. The cumulative incidence of long COVID by day 300 was 6.3% (95% CI 4.2-8.2) in participants who received metformin and 10.4% (95% CI 7.8-12.9) in those who received placebo (hazard ratio [HR] 0.59, 95% CI 0.39-0.89; P=.012).

Investigators found no effect on cumulative incidence of long COVID with ivermectin (HR 0.99, 95% CI 0.59-1.64) or fluvoxamine (HR 1.36, 95% CI 0.78-2.34) compared with placebo.

Clinical implications

"People with long COVID frequently require continued medical treatment or are unable to work for 6 months or longer. Although disease prevention is a public health challenge, taking the next steps to implement metformin as a COVID-19 treatment to prevent long COVID is an urgent public health need."

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