Can Jardiance (Empagliflozin) increase the risk of Urinary Tract Infections (UTIs)?

Jardiance (Empagliflozin) and UTI Risk

Yes, Jardiance (empagliflozin) increases the risk of urinary tract infections, including serious infections such as pyelonephritis and urosepsis that may require hospitalization. 1

Magnitude of Risk

The FDA drug label for empagliflozin explicitly warns that treatment with SGLT2 inhibitors, including Jardiance, increases the risk for urinary tract infections. 1 In large cardiovascular outcomes trials, UTI rates were:

• Placebo: 4.9% 2
• Empagliflozin: 5.7% 2

While this represents a modest absolute increase, the concern lies in the potential for serious complications rather than just uncomplicated cystitis. 1

Mechanism of Increased Risk

Empagliflozin works by blocking glucose reabsorption in the proximal renal tubules, causing intentional glucosuria (glucose in the urine). 3 This creates a glucose-rich urinary environment that theoretically favors bacterial growth. 4, 5 However, clinical data suggest the relationship between glucosuria levels and UTI incidence is not strictly dose-dependent, indicating other factors may contribute. 5

Serious Infections: The Critical Concern

The FDA issued a specific warning about serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors. 1 Postmarketing surveillance identified cases of:

• Pyelonephritis (kidney infection) 1
• Urosepsis (bloodstream infection originating from urinary tract) 1
• Septic shock requiring ICU admission 6

These serious infections can occur even in well-controlled diabetic patients without prior UTI history. 6

High-Risk Populations Requiring Extra Caution

Diabetes itself is already recognized as a complicating factor for UTIs, appearing in multiple guideline classifications of complicated UTI risk factors. 2 When combined with empagliflozin, certain patients face compounded risk:

Elderly Patients (≥75 years)

• UTI risk increases substantially: 10.5% (placebo) vs 15.7% (empagliflozin 10mg) vs 15.1% (empagliflozin 25mg) 1
• Volume depletion risk also increases, which can predispose to UTI 1

Patients with Bladder Outlet Obstruction

• Case reports document severe septicemia in men with incomplete bladder emptying and urinary stasis while on SGLT2 inhibitors 7
• Elevated post-void residual volumes create an environment conducive to bacterial colonization 7
• Caution is specifically advised when prescribing empagliflozin in this setting 7

Patients with Renal Impairment

• Those with eGFR 45-60 mL/min/1.73 m² showed increased UTI risk 1
• Renal impairment itself is a risk factor for complicated UTI 2

Recurrent UTI History

• Patients with prior chronic or recurrent genital mycotic infections are more susceptible 1
• History of UTI is a known risk factor for recurrence 8

Clinical Presentation and Monitoring

Evaluate patients promptly for signs and symptoms of urinary tract infections and treat if indicated. 1 Key symptoms include:

• Dysuria, frequency, urgency (lower UTI) 8
• Fever, flank pain, costovertebral angle tenderness (pyelonephritis) 8
• Systemic symptoms: altered mental status, malaise, rigors (urosepsis) 2

In elderly patients, atypical presentations may occur including confusion, functional decline, or behavioral changes without classic UTI symptoms. 2

Management Approach

When to Consider Discontinuation

Temporarily discontinue empagliflozin in clinical situations that predispose to complications, including acute illness with reduced oral intake or fluid losses. 1

Permanently discontinue if:

• Serious UTI develops (pyelonephritis, urosepsis) 6
• Recurrent UTIs occur after starting empagliflozin 7
• Bladder outlet obstruction with urinary stasis is identified 7

Treatment of UTI While on Empagliflozin

For complicated UTIs (which diabetes qualifies as), guidelines recommend: 2

• Urine culture and susceptibility testing before treatment 2
• Empiric therapy with combination antibiotics (amoxicillin plus aminoglycoside, second-generation cephalosporin plus aminoglycoside, or IV third-generation cephalosporin) for systemic symptoms 2
• Treatment duration of 7-14 days (14 days for men when prostatitis cannot be excluded) 2

Most UTIs associated with empagliflozin are mild to moderate and respond to standard antimicrobial treatment. 5, 3 However, serious infections require hospitalization and IV antibiotics. 6

Key Clinical Pitfalls to Avoid

• Do not dismiss UTI symptoms as "just glucosuria" - the glucose in urine is expected with empagliflozin, but symptomatic UTI requires treatment 1
• Do not continue empagliflozin through serious UTI - case reports show resolution after drug discontinuation 7, 6
• Do not overlook bladder outlet obstruction - check post-void residual in men with recurrent UTIs on empagliflozin 7
• Do not ignore atypical presentations in elderly - confusion or functional decline may be the only sign of UTI 2

Balancing Benefits and Risks

Despite the increased UTI risk, empagliflozin provides significant cardiovascular and renal benefits, including reduced hospitalizations for heart failure and cardiovascular death. 3 The absolute increase in UTI risk is modest in most patients. 2 The decision to use empagliflozin should weigh these substantial mortality benefits against UTI risk, with heightened vigilance in high-risk populations (elderly, bladder outlet obstruction, recurrent UTI history). 1, 7