What causes increased urination when taking Jardiance (Empagliflozin)?

Increased Urination with Jardiance (Empagliflozin)

Increased urination when taking Jardiance (empagliflozin) is an expected and intended effect of the medication due to its mechanism of action as an SGLT2 inhibitor that causes osmotic diuresis through increased urinary glucose excretion.

Mechanism of Action

Empagliflozin works by:

• Inhibiting sodium-glucose cotransporter 2 (SGLT2) proteins in the proximal tubules of the kidneys 1
• Blocking reabsorption of approximately 90% of filtered glucose in the kidneys 2
• Promoting glucosuria (glucose excretion in urine), which creates an osmotic diuresis effect 2, 1
• Causing both diuretic and natriuretic effects that increase urine volume 2

Clinical Effects of Increased Urination

The diuretic effect of empagliflozin leads to:

• Increased urine volume and frequency of voids 3
• Blood pressure reduction of approximately 4-5 mmHg systolic and 2-3 mmHg diastolic 1
• Weight reduction of approximately 2-3 kg, partially due to fluid loss 1, 4
• Potential volume depletion, especially when coadministered with other diuretics 3

Research Evidence

Research has demonstrated that empagliflozin significantly increases urinary excretion:

• In a study of artificially induced syndrome of inappropriate antidiuresis, empagliflozin led to significantly increased total urinary excretion (579.3 ml versus 367.3 ml with placebo) due to glucosuria 5
• The effect is more pronounced in the setting of hyperglycemia, where significant amounts of glucose are filtered into the urine 2
• Glucosuria diminishes as blood glucose normalizes, but some diuretic effect persists 2

Clinical Implications

Understanding this mechanism has important clinical implications:

1. Patient Education:

   • Patients should be informed that increased urination is expected and indicates the medication is working 1
   • Adequate hydration is important while taking this medication 1

2. Monitoring Requirements:

   • Monitor for signs of volume depletion, especially when initiating therapy 1
   • Assess for symptoms of urinary incontinence before and after SGLT2 inhibitor initiation 2
   • Be vigilant for orthostatic hypotension, particularly in older adults or those on other antihypertensive medications 2, 1

3. Cautions:

   • Use cautiously in older adults who are frail or prone to orthostasis 2
   • Consider the potential impact on patients with pre-existing urinary incontinence 2
   • Be aware that coadministration with diuretics may enhance the potential for volume depletion 3

Special Considerations

• The diuretic effect contributes to the cardiovascular benefits seen with empagliflozin, including reduced heart failure hospitalizations 2, 1
• The increased urination effect is generally well-tolerated but requires monitoring in high-risk populations 2
• Older adults may be at greater risk for clinically significant volume depletion and should be monitored more closely 2

By understanding that increased urination is a direct pharmacological effect of empagliflozin's mechanism of action, patients can be appropriately counseled and monitored to ensure safe and effective use of this medication.