Why do patients taking Jardiance (Empagliflozin) have glucose in their urine?

Why Jardiance (Empagliflozin) Causes Glucose in Urine

Jardiance (empagliflozin) intentionally causes glucose to appear in urine as its primary mechanism of action by inhibiting SGLT2 transporters in the kidneys, which prevents glucose reabsorption and promotes urinary glucose excretion. 1

Mechanism of Action

Jardiance works through a unique insulin-independent mechanism:

• SGLT2 Inhibition: Sodium-glucose co-transporter 2 (SGLT2) is the predominant transporter responsible for reabsorbing filtered glucose from the kidneys back into the bloodstream. 1
• Blocked Reabsorption: By inhibiting SGLT2, empagliflozin reduces renal glucose reabsorption and lowers the renal threshold for glucose. 1
• Increased Urinary Glucose: This results in increased urinary glucose excretion, typically 64-78 grams of glucose per day. 1

Quantifiable Effects

The glucosuria (glucose in urine) caused by Jardiance has several measurable effects:

• Glucose Excretion: Patients taking Jardiance 10 mg excrete approximately 64 grams of glucose per day in urine, while those on 25 mg excrete about 78 grams per day. 1
• Urine Volume: Mean 24-hour urine volume increases by approximately 341 mL on day 1 of treatment and stabilizes to about 135 mL above baseline by day 5. 1
• Caloric Loss: The urinary glucose excretion represents an energy loss of approximately 200-400 kcal per day. 2

Clinical Benefits of This Mechanism

The glucosuria induced by Jardiance provides several therapeutic benefits:

• Improved Glycemic Control: Reduces HbA1c by approximately 0.8% without risk of hypoglycemia (unless combined with insulin or sulfonylureas). 3
• Weight Reduction: Causes approximately 2 kg weight loss due to caloric loss through urine. 3
• Blood Pressure Reduction: Lowers systolic blood pressure by approximately 4 mmHg and diastolic by 2 mmHg through osmotic diuresis. 3
• Renal Protection: Reduces intraglomerular pressure and albuminuria, slowing GFR loss through mechanisms independent of glycemia. 4

Important Considerations

• Renal Function: The efficacy of Jardiance depends on kidney function. It is not recommended for patients with eGFR <30 mL/min/1.73 m² as the glucosuric effect diminishes with declining renal function. 2
• Genital Infections: The presence of glucose in urine increases the risk of genital mycotic infections, particularly in women. 3
• Urinary Tract Infections: There may be a slight increase in urinary tract infections due to the glucose-rich urine. 3
• Volume Depletion: The osmotic diuresis effect can potentially cause volume depletion, though the risk is generally low except in elderly or fragile patients. 2

Monitoring Recommendations

• Renal Function: Regular monitoring of kidney function is essential, especially at the initiation of treatment. 4
• Hydration Status: Patients should be monitored for signs of dehydration, particularly when starting therapy. 4
• Urinary/Genital Symptoms: Patients should report symptoms of genital or urinary tract infections promptly. 1

Jardiance represents an innovative approach to diabetes management by targeting the kidneys rather than pancreatic insulin secretion or peripheral insulin sensitivity, making glucose excretion in urine not a side effect but the intended therapeutic mechanism.