Effect of Metformin on the risk of post-COVID-19 condition among individuals with overweight and obesity in the United Kingdom: A population-based retrospective cohort study

Abstract

Background: A secondary analysis of the COVID-OUT trial showed that starting metformin within three days of a COVID-19 diagnosis and continuing it for 14 days reduced the incidence of post-COVID-19 condition (PCC) by 41% in overweight and obese individuals, compared to a placebo. However, these findings were limited to individuals aged 30-85 years, and PCC was a secondary outcome in the trial. Further studies are needed to assess whether metformin's preventive effects can be generalised to a broader population with alternative definitions of PCC. Therefore, the objective of this study was to evaluate the effectiveness of metformin in preventing the development of PCC in adults with overweight or obesity who had a recent COVID-19 infection. Method(s): We conducted a retrospective cohort study using a sequential target trial emulation framework, utilising primary care data from the Clinical Practice Research Datalink (CPRD) Aurum database (March 2020-July 2023). Adults with overweight or obesity (BMI >= 25 kg/m2) and a record of SARS-CoV-2 infection were included. Individuals with contraindications for metformin (hepatic or renal impairment or lactic acidosis) or those prescribed metformin within the year prior to diagnosis were excluded. The primary outcome was PCC, defined by a PCC diagnostic code or at least one WHO-listed symptom between 90-365 days after diagnosis, with no prior history of the symptom within 180 days before infection. We calculated the pooled hazard ratio (HR) and risk difference for the incidence of PCC, adjusting for baseline characteristics. Result(s): A total of 624,308 patients with overweight or obesity with a record of SARs-CoV-2 infection were included in the analysis. Of these, 2,976 patients who initiated metformin within 90 days after COVID-19 diagnosis date were included in the metformin treatment group. The mean age of this study cohort was 49.64 years. During follow-up, 288 metformin users and 413,686 non-users developed PCC. The estimate 1-year risk difference for PCC events in the intention-to-treat analysis was -12.58% (95% confidence interval -13.77 to -11.58%) with hazard ratio (HR) of 0.36 (95% confidence interval 0.32 to 0.41); in the per-protocol analysis it was -12.74% (95% confidence interval -13.89 to -11.76%) with HR of 0.36 (95% confidence interval 0.33 to 0.41). Subgroup and sensitivity analyses yielded consistent estimates. Conclusion(s): Our findings support the protective effect of metformin treatment within 90 days of SARS-COV-2 infection on developing PCC in people with overweight/obesity in real-world settings. Implementing metformin as an early treatment strategy for individuals with overweight or obesity and COVID-19 may be a viable approach to mitigate the risk of developing PCC, though further study is needed to evaluate its efficacy in treating PCC.