Effect of Metformin on the Risk of Post-coronavirus Disease 2019 Condition Among Individuals With Overweight or Obese: A Population-based Retrospective Cohort Study

Background: A subgroup analysis of the COVID-OUT trial's long-term outcome found that starting metformin within 3 days of coronavirus disease 2019 (COVID-19) diagnosis reduced post–COVID-19 condition (PCC) incidence by 63% in overweight or obese individuals. However, its generalizability remains uncertain. // Objectives: To evaluate the effectiveness of metformin in preventing PCC in adults with overweight or obesity who had a recent COVID-19 infection. // Design: A retrospective cohort study using a sequential target trial emulation framework. // Data Sources: The United Kingdom primary care data from the Clinical Practice Research Datalink Aurum database from March 2020 to July 2023. // Participants: Adults with overweight or obesity (body mass index ≥ 25 kg/m²) and a record of severe acute respiratory syndrome coronavirus 2 infection were included. Exclusions included metformin use in the prior year or metformin contraindications. // Measurements: The outcome was PCC, defined by a PCC diagnostic code or at least 1 World Health Organization–listed symptoms between 90 and 365 days after diagnosis, with no prior history of the symptom within 180 days before infection. The pooled hazard ratio and risk difference for the incidence of PCC were adjust for baseline characteristics. // Results: Among 624 308 patients, 2976 initiated metformin within 90 days of COVID-19 diagnosis. The 1-year risk difference for PCC in the intention-to-treat analysis was −12.58% (hazard ratio 0.36; 95% CI, 0.32–0.41), with consistent results in subgroup analyses. // Limitations: Findings may not apply to individuals with a normal body mass index. // Conclusions: Early metformin treatment in overweight or obese individuals may reduce PCC risk. Further research is needed to confirm causality and clarify metformin's role in PCC management.