A study concludes that a cheap and widely available anti-diabetes drug would reduce the risk of suffering from long Covid after infection by 40%. The work was published by the journal Lancet Infectious Diseases .
According to the World Health Organization (WHO), the so-called long Covid affects about one in 10 people who were infected with Covid-19. This disease causes long-term symptoms in those previously infected by the SARS-COV-2 virus that can range from fatigue or breathing difficulties to memory or concentration problems, cough or difficulty speaking.
The phase 3 trial tested metformin, currently the most widely used drug in the world to treat type 2 diabetes, which is also considered safe, widely available and low-cost.
It covered 1,126 overweight or obese people in the US, half treated with metformin and half with placebo in the days after testing positive for Covid-19. Ten months later, 35 of the participants who took the drug received a diagnosis of long Covid, compared to 58 in the group treated with placebo, which represents a 40% reduction in risk, the research indicates.
The team responsible for the study had previously shown that this medication reduces the risk of hospital admission and death of those infected by Covid-19 by more than 40%.
The trial was carried out between December 2020 and January 2022, so it included the omicron variant, which causes less long Covid than the previous variants. "Our data show that metformin reduces the amount of SARS-CoV-2 virus" in patients, Carolyn Bramante, a researcher at the University of Minnesota and lead author of the new study, told AFP .
But Frances Williams, professor of epidemiology at King’s College London (not involved in the study) points out that since it is a preventive method, it forces people who probably would not have contracted the disease to take medication. In the study, 564 people had to take metformin to "avoid 23 hypothetical cases" of long-Covid, she said.
Summary of the original study:
Context
Post-COVID-19 (also known as long COVID) is an emerging chronic disease that may affect millions of people. Our objective was to evaluate whether outpatient treatment of COVID-19 with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID.
Methoda
We conducted a decentralized, randomized, quadruple-blind, parallel-group Phase 3 trial (COVID-OUT) at six US sites.
We included overweight or obese adults aged 30 to 85 years who had COVID-19 symptoms for less than 7 days and a documented positive SARS-CoV-2 antigen or PCR test within 3 days before enrollment. Participants were randomly assigned using 2 × 3 parallel factorial randomization (1:1:1:1:1:1) to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Participants, investigators, care providers, and outcome assessors were unaware of study group assignment.
The primary outcome was severe COVID-19 by day 14, and that data was previously published. Because the trial was conducted remotely across the country, the a priori primary sample was intentionally modified to be untreated, meaning that participants who did not receive any doses of study treatment were excluded. Diagnosis of long COVID by a medical provider was a prespecified secondary long-term outcome.
This trial is complete and registered at ClinicalTrials.gov, NCT04510194.
Development
Between December 30, 2020 and January 28, 2022, 6,602 people were screened for eligibility and 1,431 were randomly assigned. Of 1,323 participants who received one dose of study treatment and were included in the purposefully modified-to-treat population, 1126 consented to long-term follow-up and completed at least one survey after long COVID assessment on day 180 (564 received metformin and 562 received matched placebo; a subset of participants in the metformin versus placebo trial were also assigned randomized to receive ivermectin or fluvoxamine). 1074 (95%) of 1126 participants completed at least 9 months of follow-up. 632 (56·1%) of 1126 participants were women and 494 (43·9%) were men; 44 (7·0%) of 632 women were pregnant. The median age was 45 years (IQR 37-54) and the median BMI was 29.8 kg/m2 (IQR 27.0-34.2).
Overall, 93 (8.3%) of 1,126 participants reported receiving a diagnosis of long COVID on day 300. The cumulative incidence of long COVID on day 300 was 6.3% (95% CI, 4.2– 8.2) in participants receiving metformin and 10.4% (7.8–12.9) in those receiving identical metformin placebo (hazard ratio [HR] 0.59, 95% CI 0.39 –0.89; p=0·012).
The beneficial effect of metformin was consistent in prespecified subgroups. When metformin was started within 3 days of symptom onset, the HR was 0.37 (95% CI: 0.15–0.95). There was no effect on the cumulative incidence of long COVID with ivermectin (HR 0·99, 95% CI 0·59–1·64) or fluvoxamine (1·36, 0·78–2·34) compared to placebo.
Interpretation
Outpatient metformin treatment reduced the incidence of long-term COVID by approximately 41%, with an absolute reduction of 4.1%, compared to placebo. Metformin has clinical benefits when used as an outpatient treatment for COVID-19 and is available worldwide, affordable, and safe.
Money
Parsemus Foundation; Rainwater Charitable Foundation; Fast Grants; UnitedHealth Group Foundation; National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; and National Center for Advancing Translational Sciences.
