Drug-induced hyponatremia associated with sodium-glucose cotransporter 2 inhibitors, immune checkpoint inhibitors, and targeted anticancer agents

Hyponatremia is the most common electrolyte disorder and a frequent trigger for urgent assessment in internal medicine. Beyond classic culprits, such as thiazide diuretics and antidepressants, clinicians increasingly face hyponatremia in the setting of modern metabolic and oncologic therapies. Sodium‑glucose cotransporter 2 inhibitors (notably empagliflozin and dapagliflozin) promote glucosuria‑driven osmotic diuresis and electrolyte‑free water clearance, and (based on emerging evidence) may mitigate dilutional hyponatremia in selected patients with the syndrome of inappropriate antidiuresis. At the same time, glucosuria can confound urine indices, and the diuretic effect may unmask occult hypovolemia. Immune checkpoint inhibitors (eg, nivolumab, pembrolizumab, ipilimumab) may cause hyponatremia through immune‑related endocrinopathies (secondary or primary adrenal insufficiency, thyroid dysfunction) and through nonendocrine toxicities leading to salt and water losses. In a large real‑world cohort of patients receiving immune checkpoint inhibitors, hyponatremia occurred in roughly two‑thirds, and severe hyponatremia (serum sodium