What Does SGLT2 Inhibition Add in Managing Hyponatremia Secondary to Syndrome of Inappropriate Antidiuresis (SIAD)?

Abstract

Abstract Background: Apart from treating the underlying causes, other treatment options for SIAD are of limited success. Drug repurposing of SGLT2 inhibitors for use in SIAD has been suggested. Clinical Case: A 72 years old gentleman with type 2 diabetes mellitus, hypertension, ischemic cardiomyopathy (ejection fraction 40%) and paranoid personality disorder presented with 3-day history of confusion, vomiting and reduced appetite. On examination, he was fully alert, afebrile, blood pressure 173/81 mmHg, heart rate 83 beats per minute and euvolemic. There were fine crackles in the lung bases bilaterally. Random capillary blood glucose level was 5.6 mmol/L (100 mg/dL) and there was no hypoxia. Laboratory results were suggestive of SIAD (serum sodium [Na] 115 mmol/L, serum osmolality 241 mmol/kg, urine osmolarity 458 mmol/kg, spot urine Na 56.7 mmol/L) with normal fT4 (17.6 pmol/L [1.37 ng/dL]), TSH (1.6 mIU/L) and cortisol (821 nmol/L [29.7 mcg/dL]) levels. Medications at admission were daily dosing of olanzapine 7.5 mg, sitagliptin/metformin 50/850 mg, losartan 50 mg, rosuvastatin 10 mg and aspirin 100 mg. Further investigations for causes of SIAD including magnetic resonance imaging of the brain and contrast-enhanced computed tomography of thorax, abdomen and pelvis were normal. He was treated with fluid restriction (1 liter/day) and furosemide (oral 20 mg daily for 2 doses, followed by intravenous 20 mg twice daily for 3 doses) on day 1-4, leading to negative fluid balance (total 3300 ml) with an increment in serum Na to 124 mmol/L on day 5. However, this was accompanied by a reduction in systolic blood pressure (148 to 118 mmHg) and serum potassium level (4.7 to 3.7 mmol/L), along with marked increases in urea (2.7 to 8.8 mmol/L) and creatinine levels (51 to 75 µmol/L) (eGFR from >90 to 87 mL/min/1.73m2). Hence, furosemide was stopped and empagliflozin 12.5 mg daily was initiated on day 5 with continuation of fluid restriction. Serum Na level increased by 2 mmol/L to 126 mmol/L after 12 hours and by 3 mmol/L (to 129 mmol/L) on subsequent day with negative fluid balance (950 ml per 24 hours). Urea and eGFR levels improved and losartan was reintroduced for blood pressure control. There was no euglycemic diabetic ketoacidosis episode. Patient was discharged on day 10 with a serum Na level of 131 mmol/L. Outpatient follow up 5 days after discharge showed further improvement in serum Na level to 134 mmol/L with serum osmolality 286 mmol/kg and urine osmolarity 672 mmol/kg. Clinical Lesson: SGLT2 inhibition can be considered as one of the treatment options of hyponatremia secondary to SIAD with good tolerability