SGLT2 Inhibitor (SGLT2i) as the Only Viable Treatment Option for Hyponatremia in a Patient with Cirrhosis and Ascites

Introduction: Off-label use of SGLT2 inhibitors to treat hyponatremia is not a novel concept. However, in select patients unable to tolerate salt tablets, USP urea, or tolvaptan, SGLT2i therapy may represent the only practical alternative. Case Description: On 4/23/2025, a 52-year-old man with type 2 diabetes mellitus, hypertension, alcoholic cirrhosis with ascites, and metastatic high-grade neuroendocrine carcinoma underwent a 5.5-liter paracentesis (cloudy yellow peritoneal fluid) and received intravenous albumin. He was diagnosed with malignant ascites superimposed on transudative ascites. Despite strict fluid restriction, his chronic hyponatremia (typically in the high 120s to low 130s mmol/L) worsened. Nephrology was consulted on 4/30 when serum sodium had dropped to 122 mmol/L (glucose 140 mg/dL). Urine sodium was <20 mmol/L; blood pressure remained stable (106–122/65–72 mmHg). Blood glucose ranged from 140–200 mg/dL. Serum creatinine remained stable at 0.4–0.5 mg/dL. Tolvaptan, USP urea, salt tablets, and USP urea were all contraindicated. Therefore, 10 mg/day of empagliflozin was initiated. Although urine sodium remained too low to calculate electrolyte-free water clearance, SGLT2i therapy increased urinary glucose from 6 to 1837 mg/dL—corresponding to an estimated additional osmotic load of ~100 mOsm per liter of urine. Total urine output was 2400 mL/day (based on four 6-hour collections). Serum sodium gradually increased, allowing for safe discharge. Discussion: The patient was discharged and currently his serum sodium is above 130 mmol/L in the outpatient setting. In select patients where standard therapies are contraindicated, SGLT2 inhibitors may serve as a practical and effective rescue treatment for hyponatremia in cirrhosis.