Metformin use by overweight or obese patients reduces the risk of developing long Covid by around 41%, according to the findings of a recent randomised, placebo-controlled trial.
Published in The Lancet Infectious Diseases, the study followed up on previous research which sought to determine whether the use of metformin, ivermectin or fluvoxamine prevented the primary outcome. These were the occurrence of hypoxemia, an emergency department visit, hospitalisation, or death associated with Covid-19. The researchers concluded that none of three drugs reduced the primary outcome.
For the follow-up study, the same researchers followed a subgroup of patients for 300 days to assess if any of the drugs would prevent long Covid. The participants were adults aged 30-85 years with overweight or obesity and with Covid symptoms for less than seven days. In the original trial, metformin was titrated up to a dose of 1,500 mg daily and the subsequent development of long Covid was physician diagnosed. The design of the original trial enabled a comparison of metformin use with a matching placebo and the findings of the current study largely relate to metformin.
Metformin use and long Covid
A total of 1,126 participants, 564 assigned to metformin and the remainder to matched placebo were included in the analysis. Overall, 8.3% of the cohort had developed long Covid by day 300.
The cumulative incidence of long Covid was 6.3% in the metformin group, but 10.4% (7.8-12.9) in those who received placebo (Hazard ratio, HR = 0.59, 95% CI 0.39 – 0.89 p = 0.012). In practice therefore, use of metformin reduced the absolute risk of developing long Covid by 4.1%. In other words, 24 people would need to take metformin to prevent one case of long Covid.
In the subgroup there were some interesting observations. The reduction in the risk of developing long Covid from using metformin was only significant if given less than three days from symptom onset (HR = 0.37, 95% CI 0.15 – 0.95). Similarly, the effect was also only significant in patients under 45 years of age, women and those with a body mass index greater than 30. Furthermore, metformin had no significant effect among those vaccinated against Covid-19.
Despite the positive findings, the researchers do acknowledge some limitations. Firstly, it is unclear if their findings would be generalisable to adults of a normal weight. Secondly, with a largely white population, whether metformin would still be effective for different ethnicities is unclear.