Dapagliflozin selectively inhibits SGLT2, a protein in the proximal renal tubules responsible for reabsorbing ~90% of filtered glucose. By blocking SGLT2, it:

1. Promotes Glucosuria: Prevents glucose reabsorption, leading to urinary excretion of excess glucose (~60–80 g/day) (Lippincott).
2. Reduces Hyperglycemia: Lowers blood glucose independent of insulin, making it effective even in advanced T2DM (Lange).
3. Cardiorenal Benefits:
   • Osmotic Diuresis: Mild natriuresis reduces blood pressure and intravascular volume, alleviating cardiac workload (BNF).
   • Ketogenesis: Enhances lipolysis and ketone production, which may contribute to cardiovascular benefits (Lippincott).

1. BNF-Approved Indications:
   • Type 2 Diabetes: Adjunct to diet/exercise or combined with other agents (e.g., metformin, insulin).
   • Heart Failure with Reduced Ejection Fraction (HFrEF): Reduces hospitalization and mortality.
   • Chronic Kidney Disease (CKD): Slows progression of kidney damage (eGFR ≥25 mL/min/1.73m²).
2. Off-Label Uses:
   • Heart Failure with Preserved Ejection Fraction (HFpEF): Emerging evidence supports symptom improvement (Lange).

• Type 2 Diabetes:
  • Adults: 10 mg once daily, taken in the morning (BNF).
  • Renal Adjustment: Avoid if eGFR <25 mL/min/1.73m² (ineffective due to reduced glomerular filtration).
• Heart Failure/CKD:
  • 10 mg once daily, regardless of diabetes status (BNF).
• Administration Tips:
  • Can be taken with or without food.
  • Monitor volume status in elderly or those on diuretics.

1. • Genitourinary Infections: 5–10% risk of UTIs and genital mycotic infections (e.g., candidiasis) (BNF).
   • Volume Depletion: Symptoms include hypotension, dizziness (higher risk in elderly/renally impaired patients) (Lippincott).
2. Serious but Rare:
   • Euglycemic Diabetic Ketoacidosis (DKA): Occurs despite normal blood glucose; triggers include illness, low-carb diets (Lange).
   • Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene): Rare, life-threatening soft tissue infection (BNF).

• Contraindications:
  • Severe renal impairment (eGFR <25 mL/min/1.73m²), diabetic ketoacidosis (BNF).

• • Renal Function: Assess eGFR at baseline and periodically.
  • Ketones: Check during acute illness or symptoms of DKA (e.g., nausea, vomiting).

• • Pregnancy: Avoid (BNF category not recommended; potential fetal harm in animal studies).
  • Elderly: Monitor for dehydration and renal function.

1. Diuretics: Increased risk of volume depletion/hypotension (BNF).
2. Insulin/Sulfonylureas: May raise hypoglycemia risk; consider dose reduction (Lippincott).
3. Lithium: SGLT2 inhibitors can lower lithium levels; monitor serum concentrations (Lange).

• Generic Name: Dapagliflozin.
• Brand Names:
  • UK (BNF): Forxiga®.
  • US: Farxiga®.