SGLT2 Inhibitors as a Novel Therapeutic Strategy in SIADH-Induced Hyponatraemia: Emerging Evidence and Clinical Implications
Abstract
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a leading cause of euvolaemic hyponatraemia and remains challenging to manage due to limitations of existing therapies, including poor adherence to fluid restriction and safety concerns associated with vasopressin receptor antagonists and demeclocycline. Recent mechanistic and clinical evidence suggests that sodium-glucose cotransporter-2 (SGLT2) inhibitors may offer a novel therapeutic approach by promoting osmotic diuresis and increasing electrolyte-free water clearance. This narrative review synthesises current pathophysiological understanding and emerging clinical evidence regarding the role of SGLT2 inhibitors in SIADH-related hyponatraemia. We examine how their proximal tubular mechanism differs from conventional therapies such as loop diuretics, vaptans, and salt supplementation, and evaluate evidence from recent randomised and crossover trials demonstrating improved serum sodium and enhanced water excretion with empagliflozin and dapagliflozin. SGLT2 inhibitors represent a physiologically rational and potentially safer alternative in selected patients with SIADH, particularly where fluid restriction is poorly tolerated or ineffective. Although further large-scale studies are required to define their optimal positioning within treatment algorithms, current evidence supports their potential role as an emerging therapeutic option in SIADH management.
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