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Treatment of Refractory Syndrome of Inappropriate Antidiuresis With Sodium-Glucose Cotransporter-2 Inhibitor

Chan N, Gosmanov AR

AACE endocrinology and diabetes, 2026

Abstract

Background/objective: The objective of this report is to describe a patient with syndrome of inappropriate antidiuresis (SIAD) who was successfully treated with empagliflozin monotherapy.

Case report: A 67-year-old man with a history of squamous cell carcinoma of the larynx and hypothyroidism was evaluated for persistent hyponatremia and diagnosed with SIAD. His serum sodium level remained below 130 mEq/L despite conventional therapy, including fluid restriction, furosemide, and sodium chloride tablets. He did not tolerate urea. Empagliflozin was added to his regimen resulting in improvement of serum sodium. Over time, furosemide was tapered and discontinued, followed by cessation of sodium chloride tablets. His serum sodium level normalized and remained stable on empagliflozin monotherapy without adverse effects.

Discussion: Empagliflozin, a sodium-glucose cotransporter-2 inhibitor exerts its diuretic effects through inhibition of the corresponding channel at the proximal renal tubules, which is responsible for reabsorbing most filtered glucose. Inhibiting this channel, it produces an osmotic effect without the proportional sodium loss seen with loop diuretics. Conventional therapies for SIAD often yield only modest improvements in serum sodium with response rates below 50%. Notably, 2 recent proof-of-concept studies demonstrated that adding a sodium-glucose cotransporter-2 inhibitor to fluid restriction resulted in a statistically significant increase in serum sodium…

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