This study was aimed to investigate the metabolic effects of SGLT2 inhibitors in DKD via liquid chromatography with tandem mass spectrometry (LC–MS/MS)-based metabolomic and proteomic analyzes of serum and the kidneys, and to provide a deeper understanding of the renoprotective mechanism of SGLT2 inhibitors. The gene discussed is SLC5A2; the disease is diabetic kidney disease.