SGLT2i such as empagliflozin and dapagliflozin reduce heart failure hospitalization, chronic kidney disease progression, MACE, blood pressure, and body weight by activating AMPK/mTOR pathways, inhibiting NHE3 and RAAS, and reducing oxidative stress through enhanced glucose and sodium excretion, thereby alleviating cardiac and renal stress, improving mitochondrial efficiency, and decreasing fibrosis and inflammation. The gene discussed is SLC9A3; the disease is chronic kidney disease.