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

• • Dapagliflozin
• • Empagliflozin
• • Sotagliflozin

All share similar cardiorenal benefits.

• 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.

→ Heart Failure Module

• 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:

• GLP-1 Receptor Agonists

SGLT2 inhibitors: • Strong heart failure benefit • Strong renal protection • Mild diuretic effect

GLP-1 receptor agonists: • Greater weight loss • Stronger atherosclerotic benefit

✔ 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