Empagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor used for diabetes, heart failure, and chronic kidney disease.

It was the first SGLT2 inhibitor to demonstrate cardiovascular mortality reduction.

→ SGLT2 Inhibitors Overview

Location: • Proximal convoluted tubule

Action: • Blocks SGLT2 transporter • Increases urinary glucose excretion • Causes mild natriuresis • Reduces intraglomerular pressure

Physiologic effects:

• ↓ Blood glucose • ↓ Preload (mild diuretic effect) • ↓ Blood pressure • ↓ Renal hyperfiltration • Improved cardiac efficiency

Cardiorenal benefits extend beyond glycemic control.

• Glycemic control • Reduces major adverse cardiovascular events • Promotes modest weight loss

Indicated for:

• HFrEF • HFpEF

Benefits:

• ↓ HF hospitalization • ↓ Cardiovascular mortality • Effective with or without diabetes

Part of the Four Pillars of GDMT in HFrEF.

→ Heart Failure Module

• Slows decline in GFR • Reduces albuminuria • Reduces risk of kidney failure

EMPA-REG OUTCOME:

• Reduced cardiovascular death • Reduced HF hospitalization

EMPEROR-Reduced:

• Benefit in HFrEF

EMPEROR-Preserved:

• Benefit in HFpEF

Common:

• Genital mycotic infections • Polyuria • Volume depletion • Hypotension

Serious (rare):

• Euglycemic DKA • Fournier gangrene

• Type 1 diabetes • Severe dehydration • Advanced renal failure (indication-dependent)

Hold during:

• Acute illness • Major surgery • Prolonged fasting

Dapagliflozin:

• Strong HF data (DAPA-HF) • Strong CKD data (DAPA-CKD)

Empagliflozin:

• First to show CV mortality reduction • Similar HF and renal benefit

Clinically interchangeable in most HF patients.

✔ First SGLT2 inhibitor to reduce CV mortality ✔ Effective in HFrEF and HFpEF ✔ Slows CKD progression ✔ Benefits independent of diabetes ✔ Mild diuretic effect ✔ Hold during acute illness

Related:

→ Heart Failure Module → SGLT2 Inhibitors Overview → Cardiovascular Modules