Does Empagliflozin (Jardiance) increase the risk of urinary tract infections (UTIs)?

Does Empagliflozin Increase the Risk of Urinary Tract Infections?

Yes, empagliflozin modestly increases the risk of urinary tract infections (UTIs), with the FDA-approved label reporting UTI incidence of 7.6-9.3% with empagliflozin versus 7.6% with placebo in pooled clinical trials, and this risk is higher in women, elderly patients, and those with prior UTI history. 1

Magnitude of Risk

The UTI risk with empagliflozin is real but relatively modest:

• In pooled placebo-controlled trials, UTI rates were 7.6% (placebo), 7.6% (empagliflozin 10 mg), and 9.3% (empagliflozin 25 mg) 1
• Female patients experience higher rates: 16.6% (placebo), 18.4% (empagliflozin 10 mg), and 17.0% (empagliflozin 25 mg) 1
• Male patients have lower rates: 3.2% (placebo), 3.6% (empagliflozin 10 mg), and 4.1% (empagliflozin 25 mg) 1
• Patients ≥75 years old had UTI rates of 10.5% (placebo), 15.7% (empagliflozin 10 mg), and 15.1% (empagliflozin 25 mg) 1

Real-world observational data from Thailand showed higher UTI incidence (33.03% with empagliflozin vs 11.72% with non-SGLT2 inhibitors), though this may reflect different patient populations and detection methods 2

Mechanism of Increased Risk

The persistent glucosuria created by empagliflozin's mechanism of action produces a glucose-rich environment in the genitourinary tract that promotes bacterial growth. 3 This osmotic diuresis increases urine volume and frequency, which paradoxically may both increase exposure to pathogens and potentially help flush bacteria 3

High-Risk Populations Requiring Caution

Female gender is the strongest risk factor, with approximately 3-5 times higher UTI rates than males across all treatment groups 1

Advanced age (≥75 years) increases UTI risk substantially, with rates reaching 15-16% in elderly patients on empagliflozin 1

Patients with chronic or recurrent UTI history are more likely to experience UTIs on empagliflozin 1

Male patients with bladder outlet obstruction or incomplete bladder emptying may face increased risk, as case reports document serious urosepsis in this setting 4 The FDA label includes postmarketing reports of urosepsis and pyelonephritis 1

Patients using indwelling catheters were previously thought to be at higher risk, but a Veterans Affairs study found no statistically significant increase in UTI rates when comparing catheter use alone versus concurrent catheter and empagliflozin use (0.09 UTIs/month pre-empagliflozin vs 0.07 post-empagliflozin, P=0.61) 5

Clinical Management Algorithm

Do not withhold empagliflozin solely due to UTI concerns in most patients, as the cardiovascular and renal protective benefits substantially outweigh the modest UTI risk 6

For patients initiating empagliflozin:

• Screen for history of recurrent UTIs (≥3 episodes in past year) 1
• In males, assess for urinary retention symptoms or known prostatic obstruction 4
• Counsel all patients, especially women and elderly, about UTI symptoms (dysuria, frequency, urgency, suprapubic pain) 1
• Consider baseline urinalysis in high-risk patients 2

If UTI develops on empagliflozin:

• Treat the UTI with appropriate antibiotics per standard guidelines 1
• Discontinuation rate due to UTI was only 0.1-0.2% in clinical trials, indicating most UTIs can be managed without stopping the drug 1
• Continue empagliflozin during and after UTI treatment unless complicated infection (pyelonephritis, urosepsis) develops 1

Consider discontinuation only if:

• Recurrent complicated UTIs (pyelonephritis, urosepsis) occur 1
• Male patient develops urinary retention or has significant bladder outlet obstruction 4
• Patient experiences ≥3 UTIs within 6 months of starting empagliflozin 2

Critical Context: Benefits Outweigh Risks

The American Diabetes Association recommends continuing empagliflozin even when eGFR falls below 45 mL/min/1.73 m² for cardiovascular and kidney benefits, despite minimal glucose-lowering effects at these levels. 6, 3 This recommendation reflects that empagliflozin reduces:

• Incident or worsening nephropathy by 39% 6
• Doubling of serum creatinine with eGFR ≤45 mL/min/1.73 m² by 44% 6
• Cardiovascular death by 38% in the EMPA-REG OUTCOME trial 6
• Heart failure hospitalization by 35% 6

These mortality and morbidity benefits far exceed the inconvenience and manageable risk of UTIs in the vast majority of patients. 6

Common Pitfall to Avoid

Do not confuse genital mycotic infections with UTIs—genital mycotic infections (vaginal candidiasis, balanitis) are more common than UTIs with empagliflozin (4.1% for 10 mg, 3.7% for 25 mg vs 0.9% placebo) but are distinct conditions requiring different management 1 Genital infections occur in approximately 6% of SGLT2 inhibitor users versus 1% on placebo 3