SGLT2 inhibitors are sodium-glucose cotransporter-2 inhibitors that act in the proximal tubule of the kidney.
Originally developed for Type 2 Diabetes, they are now foundational therapies in:
• Heart Failure • Chronic Kidney Disease • Type 2 Diabetes Mellitus
Their cardiovascular and renal benefits extend beyond glucose lowering.
Location: • Proximal convoluted tubule
Normal physiology: • SGLT2 reabsorbs ~90% of filtered glucose • Sodium and glucose are co-transported
Drug effect: • Blocks SGLT2 • Increases urinary glucose excretion • Causes mild natriuresis • Reduces intraglomerular pressure
Net physiologic effects: • ↓ Blood glucose • Mild osmotic diuresis • ↓ Preload • ↓ Blood pressure • ↓ Cardiorenal stress
• Improve glycemic control • Promote modest weight loss • Reduce cardiovascular events
Indicated for:
• HFrEF • HFpEF
Benefits: • ↓ Heart failure hospitalization • ↓ Cardiovascular mortality • Effective regardless of diabetes status
Part of the Four Pillars in HFrEF.
• Slows progression of CKD • Reduces albuminuria • Preserves GFR
Renal benefit independent of diabetes.
Common:
• Genital mycotic infections • Polyuria • Volume depletion • Hypotension
Serious (rare):
• Euglycemic DKA • Fournier gangrene
• Type 1 diabetes (DKA risk) • Severe volume depletion • Advanced renal impairment (varies by agent)
Hold during acute illness or prolonged fasting.
Compared to:
SGLT2 inhibitors:
GLP-1 receptor agonists:
✔ Act in the proximal tubule ✔ Mild diuretic effect ✔ Reduce HF hospitalization ✔ Slow CKD progression ✔ Benefit independent of diabetes status ✔ One of the Four Pillars of HFrEF
Related:
→ Heart Failure Module → Cardiovascular Modules → Endocrine Pharmacology