====== 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.

→ [[endocrine:sglt2:start|SGLT2 Inhibitors Overview]]

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===== 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

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===== Indications =====

==== Type 2 Diabetes Mellitus ====

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

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==== 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.

→ [[cardio:heart_failure:start|Heart Failure Module]]

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==== Chronic Kidney Disease ★ ====

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

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===== Major Trials =====

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

DELIVER:
• Benefit in HFpEF

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

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===== Adverse Effects =====

Common:

• Genital mycotic infections
• Polyuria
• Hypotension
• Volume depletion

Serious (rare):

• Euglycemic diabetic ketoacidosis
• Fournier gangrene

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===== Contraindications / Cautions =====

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

Hold during:

• Acute illness
• Major surgery
• Prolonged fasting

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===== Dapagliflozin vs Other SGLT2 Inhibitors =====

[[endocrine:sglt2:empagliflozin|Empagliflozin]]:
• Similar HF and CKD benefit

[[endocrine:sglt2:sotagliflozin|Sotagliflozin]]:
• Also inhibits SGLT1
• Broader GI glucose effect

All SGLT2 inhibitors provide:

• Heart failure benefit
• Renal protection
• Modest glucose lowering

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===== Clinical Pearls =====

✔ Reduces HF hospitalization  
✔ Works