Therefore, we propose that DAPA likely alleviates renal fibrosis in DKD by modulating renal TGF-β1 activity and restoring the Smad3/Smad7 balance, thereby suppressing MMT.<h4>Conclusion</h4>This study is the first to reveal that DAPA is highly likely to exert anti-fibrotic effects through a novel mechanism involving targeted modulation of the TGF-β1-Smad3/7 axis to inhibit MMT, thereby laying a theoretical foundation and identifying a potential therapeutic target for precision treatment of DKD. This evidence concerns the gene SMAD7 and renal fibrosis.