How does Farxiga (dapagliflozin) help reduce water weight?

How Farxiga Reduces Water Weight

Farxiga (dapagliflozin) reduces water weight primarily by inhibiting sodium-glucose cotransporter-2 (SGLT2) in the proximal renal tubules, which promotes urinary glucose excretion and reduces sodium reabsorption, leading to mild osmotic diuresis and natriuresis. 1

Mechanism of Action

Farxiga works through a unique mechanism that affects water balance in the body:

1. SGLT2 Inhibition: Dapagliflozin selectively inhibits SGLT2 in the proximal renal tubules 1

   • SGLT2 is responsible for approximately 90% of glucose reabsorption in the kidneys
   • By blocking this transporter, filtered glucose remains in the tubular lumen

2. Osmotic Diuresis Effect:

   • The increased urinary glucose creates an osmotic effect that draws water into the urine 1
   • This results in increased urine volume and fluid loss from the body

3. Sodium Excretion:

   • Dapagliflozin reduces sodium reabsorption in the proximal tubule 1
   • Increases delivery of sodium to the distal tubule
   • Promotes natriuresis (sodium excretion in urine)

Quantifiable Effects on Water Weight

• Clinical studies show that dapagliflozin doses of 5-10 mg per day result in excretion of approximately 70 grams of glucose in urine daily 1
• This urinary glucose excretion directly increases urinary volume 1
• After discontinuation of dapagliflozin, the elevation in urinary glucose excretion typically returns to baseline within about 3 days 1

Impact on Body Composition

Research demonstrates that the weight loss from dapagliflozin comes from multiple sources:

• In a 24-week study, dapagliflozin produced a placebo-corrected total body weight reduction of 2.08 kg 2
• This weight loss was predominantly from:
  • Fat mass reduction: -1.48 kg 2
  • Reduction in visceral adipose tissue: -258.4 cm³ 2
  • Reduction in subcutaneous adipose tissue: -184.9 cm³ 2
  • Water weight reduction through diuretic effect 1

Clinical Applications for Water Retention

Farxiga's effect on water weight makes it particularly valuable in certain clinical scenarios:

• Heart Failure Management:

  • SGLT2 inhibitors reduce hospitalization rates for heart failure regardless of diabetes status 3
  • They improve congestion status and can reduce the need for loop diuretics 4
  • In the EMPULSE trial, empagliflozin (another SGLT2 inhibitor) showed significant improvements in markers of decongestion 4

• Chronic Kidney Disease:

  • Dapagliflozin is approved to reduce the risk of declining kidney function, kidney failure, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease 5
  • The diuretic effect helps manage fluid overload in these patients

Practical Considerations

When using Farxiga for water weight reduction:

• Monitoring: Watch for symptoms of volume depletion, especially when initiating therapy
• Diuretic Adjustment: Consider reducing doses of other diuretics when starting Farxiga to prevent excessive fluid loss 3
• Duration of Effect: The diuretic effect begins quickly but may take several days to fully manifest
• Return to Baseline: After discontinuation, urinary glucose excretion typically returns to baseline within about 3 days 1

Potential Side Effects Related to Diuretic Effect

• Volume depletion/hypotension, particularly in elderly patients or those on other diuretics 3
• Increased risk of genital mycotic infections due to glucose in the urine 3
• Electrolyte imbalances may occur due to the natriuretic effect

Farxiga's ability to reduce water weight through its unique mechanism makes it valuable not only for glycemic control but also for managing fluid overload in conditions like heart failure and chronic kidney disease.