Metformin IDd as repurposable drug for atrial fibrillation

 

• Jessica C. Lal 12
• Chengsheng Mao 12
• Yadi Zhou
• Yuan Luo
• Feixiong Cheng 10
• Mina K. Chung 11, 13
                                                                                                                            
• DOI:
  https://doi.org/10.1016/j.xcrm.2022.100749
  
  
  
                                                                                    

• Highlights

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    Network proximity analysis predicts metformin as repurposed drug for AF
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    Metformin induces directional changes in AF disease module genes
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    Large-scale health record data support metformin use for reduced AF risk

  Summary

  Effective drugs for atrial fibrillation (AF) are lacking, resulting in significant morbidity and mortality. This study demonstrates that network proximity analysis of differentially expressed genes from atrial tissue to drug targets can help prioritize repurposed drugs for AF. Using enrichment analysis of drug-gene signatures and functional testing in human inducible pluripotent stem cell (iPSC)-derived atrial-like cardiomyocytes, we identify metformin as a top repurposed drug candidate for AF. Using the active compactor, a new design analysis of large-scale longitudinal electronic health record (EHR) data, we determine that metformin use is significantly associated with a reduced risk of AF (odds ratio = 0.48, 95%, confidence interval [CI] 0.36–0.64, p < 0.001) compared with standard treatments for diabetes. This study utilizes network medicine methodologies to identify repurposed drugs for AF treatment and identifies metformin as a candidate drug.
• https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(22)00298-1
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