How to manage dysuria in a patient taking Jardiance (empagliflozin) for diabetes with no evidence of urinary tract infection (UTI)?

Management of Dysuria in Patients Taking Jardiance (Empagliflozin) with Negative UTI Workup

In patients taking empagliflozin who develop dysuria with negative urine cultures, implement hygienic counseling to prevent genital mycotic infections, increase fluid intake to dilute urine and reduce irritation, and avoid potential urinary irritants—while continuing the SGLT2 inhibitor unless symptoms are severe or persistent. 1, 2

Understanding the Clinical Context

Empagliflozin causes glucosuria by blocking glucose reabsorption in the proximal renal tubule, resulting in 50-100g of glucose lost in urine per 24 hours. 3, 4 This creates an environment conducive to genital mycotic infections, which occur more frequently especially in women, though urinary tract infections themselves show only negligible increases and are typically mild. 3, 4

The dysuria in this scenario is most likely related to:

• Genital mycotic infection (most common SGLT2 inhibitor-related cause) 1, 3
• Osmotic diuresis-related urethral irritation from glucosuria 3, 4
• Underlying diabetic bladder dysfunction (diabetic cystopathy), which affects up to 80% of type 1 diabetic patients and 25% of type 2 diabetic patients 1

Immediate Management Steps

Rule Out Genital Mycotic Infection

• Perform a thorough genital examination looking for erythema, discharge, or candidal lesions, as mycotic genital infections are the most common side effect of SGLT2 inhibitors. 1, 3
• If genital mycotic infection is confirmed, treat with topical antifungal therapy while continuing empagliflozin. 1
• Provide hygienic counseling to prevent recurrence, as recommended for SGLT2 inhibitor risk mitigation. 1

Implement Non-Pharmacological Interventions

• Increase fluid intake to dilute urine and reduce irritation from concentrated glucosuric urine. 2
• Avoid potential irritants including spermicides, douches, and scented hygiene products. 2
• Counsel on proper perineal hygiene, particularly important given the glucosuria-rich environment. 1

Assess for Diabetic Bladder Dysfunction

Since diabetic patients commonly develop bladder complications, evaluate for:

• Symptoms of diabetic cystopathy: frequency, urgency, nocturia, incomplete bladder emptying, infrequent voiding, poor stream, or hesitancy. 1
• Post-void residual (PVR) volume using portable ultrasound to avoid catheterization-related infection risk. 1
• Urodynamic testing if initial management fails or diagnosis remains uncertain. 1

Diabetic bladder dysfunction can manifest as detrusor overactivity (48% of cases), impaired detrusor contractility (30%), or poor compliance (15%), all of which can cause dysuria-like symptoms. 1

Decision Algorithm for Continuing Empagliflozin

Continue empagliflozin if:

• Dysuria is mild to moderate 1
• No signs of severe dehydration or hypotension 1, 4
• Patient responds to conservative measures 1
• eGFR remains ≥20 mL/min/1.73 m² 1

The KDIGO 2024 guidelines emphasize that SGLT2 inhibitor initiation does not necessitate alteration of monitoring frequency, and the reversible decrease in eGFR on initiation is generally not an indication to discontinue therapy. 1

Temporarily withhold empagliflozin if:

• Severe, persistent dysuria unresponsive to treatment 1
• Signs of volume depletion or hypotension develop 1, 4
• Patient requires prolonged fasting, surgery, or experiences critical medical illness (increased ketosis risk) 1

Special Considerations for Diabetic Patients

Diabetic Bladder Dysfunction Management

If diabetic cystopathy is identified:

• For acontractile bladder: Intermittent catheterization remains the treatment of choice. 1
• For overactive bladder symptoms: Consider urotherapy including education about bladder/bowel function, timed voiding schedules, adequate fluid intake, and management of constipation. 2
• Measure PVR and perform urine dipstick yearly in all insulin-dependent diabetic patients. 1

Excluding Other Causes

• Confirm negative urine culture was obtained properly, as diabetic patients have increased susceptibility to infections, particularly E. coli. 1
• In postmenopausal women, consider hypoestrogenism as a cause; vaginal estrogen replacement is strongly recommended if this is identified. 2, 5
• Assess for urethral obstruction from benign prostatic hyperplasia in men, though similar symptoms may result from bladder denervation and poor detrusor contractility in diabetic patients. 1

Common Pitfalls to Avoid

• Do not treat asymptomatic bacteriuria in diabetic patients, as this leads to antimicrobial resistance without clinical benefit. 1
• Do not discontinue empagliflozin prematurely based solely on mild dysuria, as the cardiovascular and renal benefits are substantial. 1, 6
• Do not assume all dysuria is infectious in diabetic patients taking SGLT2 inhibitors; genital mycotic infections and diabetic bladder dysfunction are more likely culprits. 1, 3
• Do not ignore the transient diuretic effect of empagliflozin, which peaks at day 1 but returns to baseline within 4 weeks without causing clinically significant dehydration in patients under 60 years. 7

Monitoring and Follow-Up

• Reassess symptoms within 1-2 weeks of implementing conservative measures. 2
• If dysuria persists despite negative cultures and conservative management, consider urodynamic evaluation to assess for diabetic cystopathy. 1
• Monitor for recurrent genital mycotic infections, which may require prophylactic antifungal therapy if frequent. 1
• Continue empagliflozin unless contraindicated, as interruption or discontinuation due to UTI-related symptoms is rare and SGLT2 inhibitors do not increase risk of severe infections like urosepsis or pyelonephritis. 8