Early Metformin Use Lowers Long COVID Risk, Finds Study
UK: A large UK target trial emulation using COVID-OUT trial data found that early use of metformin reduced the risk of long COVID by 36% at 1 year among overweight or obese adults. This supports findings from a 2023 Phase 3 trial by the University of Minnesota, which showed that a 14-day metformin regimen reduced the risk of long COVID by 63% at 10 months when initiated within 3 days of symptom onset in patients aged 30–85 years.
The latest study, published in Clinical Infectious Diseases, was led by Dr. Ubonphan Chaichana and colleagues from the Research Department of Practice and Policy, UCL School of Pharmacy, London. The investigators aimed to assess whether the protective effects of metformin observed in the COVID-OUT trial could be generalized to a broader population using real-world UK data.
For the study, researchers conducted a retrospective cohort analysis using the Clinical Practice Research Datalink Aurum database, spanning the period from March 2020 to July 2023. The population included adults with a body mass index (BMI) of 25 kg/m² or higher who had a documented COVID-19 infection. Patients who had used metformin in the year before diagnosis or had contraindications to the drug were excluded.
The outcome of interest was the development of post–COVID-19 condition (PCC), commonly referred to as long COVID. PCC was defined by the presence of a diagnostic code or at least one World Health Organization–recognized symptom occurring 90 to 365 days after infection, with no record of the symptom in the preceding six months.
The following were the key findings of the study:
- A total of 624,308 individuals met the inclusion criteria.
- Among them, 2,976 initiated metformin within 90 days of COVID-19 diagnosis.
- The intention-to-treat analysis showed that metformin use was linked to a 36% reduction in the risk of developing post–COVID-19 condition (PCC).
- The hazard ratio for PCC was 0.36.
- The absolute risk difference was −12.58%.
- Subgroup analyses confirmed consistent results across different patient categories.
The authors highlighted that these findings reinforce the potential of metformin as a low-cost, widely available option to lower the likelihood of long COVID in overweight and obese populations. Importantly, the results mirror those from controlled clinical trials, suggesting that the benefit extends beyond trial settings into routine clinical practice.
However, the study had limitations. Since only overweight or obese adults were included, the findings may not apply to individuals with normal BMI. Additionally, as this was an observational analysis, the authors caution that causality cannot be fully established.
"The study indicates that starting metformin early after a COVID-19 diagnosis could substantially reduce the risk of long COVID in adults with excess body weight. The authors call for further randomized controlled trials to confirm the causal relationship and to better define metformin’s role in long COVID prevention strategies," the authors concluded.
Reference:
Chaichana, U., Man, K. K., Ju, C., Makaronidis, J., & Wei, L. Effect of Metformin on the Risk of Post-coronavirus Disease 2019 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study. Clinical Infectious Diseases. https://doi.org/10.1093/cid/ciaf429
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