Dapagliflozin

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

It provides cardiovascular and renal benefit independent of glucose lowering.

SGLT2 Inhibitors Overview


Mechanism of Action

Location: • Proximal convoluted tubule

Action: • Blocks SGLT2 transporter • Decreases glucose reabsorption • Increases urinary glucose excretion • Causes mild natriuresis

Physiologic effects: • ↓ Blood glucose • ↓ Intravascular volume • ↓ Blood pressure • ↓ Intraglomerular pressure • Improved cardiac energy efficiency


Indications

Type 2 Diabetes Mellitus

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


Heart Failure ★

Indicated for:

• HFrEF • HFpEF

Benefits: • ↓ HF hospitalization • ↓ Cardiovascular mortality • Effective in patients with or without diabetes

Part of the Four Pillars of GDMT in HFrEF.

Heart Failure Module


Chronic Kidney Disease ★

• Slows CKD progression • Reduces risk of dialysis • Reduces albuminuria • Reduces cardiovascular events


Major Trials

DAPA-HF: • Reduced HF hospitalization • Reduced cardiovascular death

DELIVER: • Benefit in HFpEF

DAPA-CKD: • Slowed CKD progression • Reduced renal failure


Adverse Effects

Common:

• Genital mycotic infections • Polyuria • Hypotension • Volume depletion

Serious (rare):

• Euglycemic diabetic ketoacidosis • Fournier gangrene


Contraindications / Cautions

• Type 1 diabetes (DKA risk) • Severe dehydration • Advanced renal failure (threshold varies by indication)

Hold during:

• Acute illness • Major surgery • Prolonged fasting


Dapagliflozin vs Other SGLT2 Inhibitors

Empagliflozin: • Similar HF and CKD benefit

Sotagliflozin: • Also inhibits SGLT1 • Broader GI glucose effect

All SGLT2 inhibitors provide:

• Heart failure benefit • Renal protection • Modest glucose lowering


Clinical Pearls

✔ Reduces HF hospitalization ✔ Works