Is glucosuria expected in patients taking Jardiance (empagliflozin)?

Is Glucosuria Expected with Jardiance (Empagliflozin)?

Yes, glucosuria is not only expected but is the primary mechanism of action by which Jardiance (empagliflozin) works. This is an intentional therapeutic effect, not an adverse reaction.

Mechanism of Action

Empagliflozin works by inhibiting SGLT2 (sodium-glucose cotransporter 2) in the renal proximal tubules, which directly reduces glucose reabsorption and increases urinary glucose excretion. 1 This is the fundamental way the medication achieves its therapeutic benefits across multiple conditions including type 2 diabetes, heart failure, and chronic kidney disease.

Quantifiable Glucosuria

The amount of glucose excreted in urine is substantial and dose-dependent:

• 10 mg empagliflozin: approximately 64 grams of glucose per day 1
• 25 mg empagliflozin: approximately 78 grams of glucose per day 1

This glucosuria begins immediately after the first dose and is maintained throughout treatment. 1

Clinical Implications for Laboratory Testing

Patients and clinicians should expect elevated glucose in urinalysis when taking Jardiance—this is the intended effect and confirms the medication is working. 1 The FDA label explicitly states that "elevated glucose in urinalysis is expected when taking JARDIANCE." 1

Important Monitoring Considerations

• Do not use urine glucose testing to monitor diabetes control in patients on SGLT2 inhibitors 1
• Blood glucose and HbA1c measurements remain the appropriate methods for assessing glycemic control 1
• The glucosuria is therapeutic, not pathologic, and does not indicate poor diabetes control 1

Associated Effects of Glucosuria

The glucosuria induced by empagliflozin produces several secondary effects:

Osmotic Diuresis

The glucose in urine creates an osmotic effect that increases urine volume, particularly in the first few days of treatment. 2 In Japanese patients with type 2 diabetes, 24-hour urine volume increased by approximately 0.83-1.08 L/day on day 1 with the 10-25 mg doses. 2 However, this diuretic effect is transient—urine volume returns to near-baseline levels within 4 weeks as the body adapts. 2

Caloric Loss and Weight Reduction

The urinary loss of approximately 64-78 grams of glucose daily represents a caloric loss of roughly 250-310 calories per day, contributing to the weight reduction observed with empagliflozin. 3 This typically results in approximately 2 kg of weight loss. 3

Natriuretic Effect

Empagliflozin has both diuretic and natriuretic effects, promoting sodium excretion along with glucose. 4 This contributes to blood pressure reduction of approximately 4 mmHg systolic and 2 mmHg diastolic. 3

Safety Considerations Related to Glucosuria

Volume Depletion Risk

The osmotic diuresis from glucosuria can lead to volume depletion, particularly in high-risk populations. 1 High-risk groups include:

• Elderly patients (≥65 years) 1
• Patients on concurrent diuretic therapy 1
• Patients with low blood pressure 1
• Those on low sodium diets 1
• Patients with kidney problems 1
• Care-dependent patients who cannot autonomously replace fluid losses 5

Patients should be counseled to watch for signs of volume depletion including orthostatic lightheadedness, dizziness, or feeling faint when standing. 1 However, it is important to note that preemptive discontinuation or dose reduction of concurrent diuretics is usually not necessary when initiating empagliflozin. 4

Genitourinary Infections

The persistent glucosuria creates a glucose-rich environment in the genitourinary tract, increasing the risk of mycotic genital infections, particularly in women. 6, 3 Genital mycotic infections occur in approximately 6% of patients on SGLT2 inhibitors versus 1% on placebo. 6

Contrary to initial concerns, the relationship between glucosuria and urinary tract infections is minimal. 7 Analysis of dapagliflozin trials showed that while urinary glucose levels increased progressively with dosage, the incidence of urinary tract infections did not show a definitive dose relationship. 7 Most infections are mild to moderate and respond to standard antimicrobial treatment. 7

Severe Dehydration in Vulnerable Populations

A critical pitfall is initiating or continuing empagliflozin in patients who have lost the ability to autonomously replace fluid losses. 5 A case report documented severe hypernatremic dehydration (sodium 164 mmol/L) and unconsciousness in a stroke patient who became care-dependent and could not communicate thirst. 5 The persistent glucosuria (3935 mg/dL in urine) led to progressive volume depletion. 5

In patients who depend on others for fluid intake, have impaired sense of thirst, or cannot communicate thirst, SGLT2 inhibitor therapy should not be initiated or should be temporarily discontinued. 5

Efficacy Considerations

The glucose-lowering efficacy of empagliflozin increases with the degree of hyperglycemia but decreases in patients with renal insufficiency. 3 This is because glucosuria depends on glomerular filtration of glucose—as kidney function declines, less glucose is filtered and available for SGLT2 inhibition. 6

However, empagliflozin should be continued even when eGFR falls below initiation thresholds (≥20 mL/min/1.73 m²) for its cardiovascular and renal protective benefits, despite diminished glucose-lowering effects. 6