Sodium–glucose cotransporter 2 inhibitors for hypertension in cardiovascular–kidney–metabolic syndrome

The antihypertensive mechanism of sodium-glucose cotransporter 2 (SGLT2) inhibitors has been traditionally attributed to osmotic diuresis. However, emerging evidence reveals multifaceted mechanisms beyond diuresis, including regulation of the renin-angiotensin-aldosterone system, sympathetic nervous system suppression, ion homeostasis restoration, anti-inflammatory/antioxidant actions, weight loss and improved vascular function. These synergistic pathways collectively reduce blood pressure and provide cardiorenal protection in cardiovascular-kidney-metabolic (CKM) syndrome patients. Elucidating these multi-target antihypertensive effects holds critical implications for optimizing therapeutic strategies, mitigating cardiorenal risks and establishing SGLT2 inhibitors as adjunctive antihypertensive therapy in CKM syndrome patients.