Treating COVID with Metformin
In a groundbreaking study published in Lancet Infectious Diseases, researchers have found that metformin, a widely available and affordable diabetes drug, could potentially reduce the incidence of long COVID when administered during the acute phase of COVID-19. This randomised controlled trial demonstrated that a two-week course of metformin, initiated within three days of testing positive for SARS-CoV-2, resulted in 40% fewer long COVID diagnoses over the following 10 months compared to individuals who received a placebo.
The Study and its Findings
The trial involved 1126 participants who had tested positive for SARS-CoV-2 in the previous three days but had no known prior COVID-19 infection. These individuals were at a higher risk of developing severe COVID-19 due to being overweight or obese. The median age of the participants was 45 years, with 44% being male and 56% female.
The participants were randomly assigned to receive either a placebo or metformin, which was gradually increased from 500 mg to 1000 mg over a six-day period. Follow-up surveys were conducted on days 180, 210, 240, 270, and 300 to ascertain whether a medical provider had diagnosed them with long COVID. The study authors selected this method to determine long COVID as the definition of the condition changed throughout the study period.
The cumulative incidence of long COVID by day 300 was found to be 6.3% (35 out of 564) in the group that received metformin, compared to 10.4% (58 out of 562) in the placebo group. The hazard ratio of 0.59 (95% confidence interval 0.39-0.89) indicated a statistically significant reduction in the risk of long COVID with metformin administration. Notably, the protective effect of metformin was potentially greater when initiated within three days of symptom onset.
Implications and Significance
This study is the first to suggest that drugs administered during the acute phase of COVID-19 could potentially reduce the risk of long COVID. The symptoms of long COVID, such as breathlessness, chronic fatigue, “brain fog,” anxiety, and stress, can be debilitating and persist for an extended period. Currently, there are no proven treatments or preventive measures for long COVID, except for reducing the risk of initial infection.
The urgency to find potential treatments and preventive strategies for long COVID arises from its potential long-term physical, mental, and economic impacts, especially on socioeconomically marginalized groups. Lead study author Carolyn Bramante from the University of Minnesota Medical School emphasizes the need to address this significant public health emergency. Metformin, being a safe, low-cost, and widely available drug, offers a promising solution by substantially reducing the risk of long COVID if administered during the early stages of the coronavirus infection.
Jeremy Faust from Harvard Medical School, who was not involved in the research, acknowledges the profound and potentially landmark findings of this study. He emphasizes the significance of this high-quality evidence from a randomized controlled trial, indicating that the incidence of long COVID can be reduced through a medical intervention like metformin, a treatment with which clinicians have ample experience.
Mechanism of Action and Study Limitations
Although the exact mechanism by which metformin reduces the incidence of long COVID remains unclear, previous studies have demonstrated its ability to inhibit the replication of the SARS-CoV-2 virus in laboratory settings. This finding aligns with predictions from mathematical models of viral replication, suggesting that this could be the underlying cause of the observed reduction in both severe COVID-19 and long COVID diagnoses in the trial.