Risk of UTI with SGLT2 Inhibitors
Large randomized controlled trials have consistently shown no increased risk of urinary tract infections with SGLT2 inhibitors compared to placebo, despite theoretical concerns about glycosuria creating a favorable environment for bacterial growth. 1
Evidence from Major Clinical Trials
The highest quality evidence comes from cardiovascular outcome trials:
EMPA-REG OUTCOME, CANVAS, and CANVAS-R trials demonstrated no difference in rates of any urinary tract infections or serious urinary tract infections between SGLT2 inhibitors and placebo, despite millions of patient-years of exposure 1
Post-marketing surveillance has identified rare cases of serious UTIs (pyelonephritis and urosepsis requiring hospitalization), but these remain uncommon events 1, 2
Real-World Evidence Confirms Trial Findings
Recent population-based studies support the trial data:
A 2022 propensity score-matched cohort study using UK and Canadian databases found no increased UTI risk with SGLT2 inhibitors compared to DPP-4 inhibitors (HR 1.08,95% CI 0.89-1.30), sulfonylureas (HR 1.08,95% CI 0.90-1.30), GLP-1 agonists (HR 0.81,95% CI 0.61-1.09), or thiazolidinediones (HR 0.81,95% CI 0.55-1.19) 3
SGLT2 inhibitors showed lower UTI risk compared to insulin (HR 0.74,95% CI 0.63-0.87) 3
A 2024 cross-sectional study of 328 patients found no statistical difference in UTI rates between SGLT2 inhibitor users and those on other glucose-lowering medications 4
Contrast with Genital Mycotic Infections
The infection risk profile differs markedly by anatomical site:
Genital mycotic infections occur in approximately 6% of SGLT2 inhibitor users versus 1% on placebo - this represents the primary genitourinary concern 1, 5
These genital infections (candida vaginitis in women, balanitis in men) are typically mild, respond to brief antifungal courses, and rarely recur 1
Risk Factors When UTIs Do Occur
When prescribing SGLT2 inhibitors, identify patients at higher baseline UTI risk:
- Female gender - consistently associated with higher UTI rates across studies 6
- Older age - elderly patients show increased susceptibility 1, 6
- Poor glycemic control - higher HbA1c independently predicts UTI risk 4
- Higher BMI - obesity increases UTI likelihood 4
- Longer diabetes duration - correlates with UTI risk in SGLT2 inhibitor users 4
- History of recurrent UTIs - warrants cautious use 1, 5
Clinical Management Algorithm
For patients without recurrent UTI history:
- Initiate SGLT2 inhibitors without additional UTI-specific precautions 1, 3
- Counsel on proper genital hygiene to prevent mycotic infections 5
- Monitor for UTI symptoms at routine follow-up 5
For patients with recurrent or severe UTI history:
- Use SGLT2 inhibitors cautiously - the cardiovascular and renal benefits may still outweigh risks, particularly in CKD or heart failure 1, 5
- Provide thorough education on early symptom recognition 5
- Implement close monitoring during initial months 5
- Consider alternative antidiabetic agents if infections become burdensome 5
If UTI develops during SGLT2 inhibitor therapy:
- Treat with standard antibiotic therapy without discontinuing SGLT2 inhibitor for uncomplicated UTI 5
- Consider temporary discontinuation for severe or recurrent UTIs 5
- Discontinue immediately for urosepsis, pyelonephritis, or Fournier's gangrene 5, 2
FDA-Labeled Warnings
The dapagliflozin label specifically warns about urosepsis and pyelonephritis requiring hospitalization and instructs clinicians to evaluate and treat UTI signs/symptoms promptly 2. Canagliflozin labeling includes postmarketing reports of urosepsis and pyelonephritis 7.
Special Populations
Older adults: SGLT2 inhibitors should be used cautiously in frail elderly or those prone to orthostasis due to volume depletion risk, but UTI risk alone should not preclude use 1
Non-diabetic patients: A 2023 meta-analysis found increased odds of UTI in non-diabetic patients taking SGLT2 inhibitors (OR 1.33,95% CI 1.13-1.57), though the absolute risk remains lower than in diabetic patients 8
Common Pitfall to Avoid
Do not confuse genital mycotic infections with UTIs - the former are common (6% incidence) and expected, while true UTIs show no increased incidence in high-quality trials 1, 5. Counsel patients specifically about genital hygiene and yeast infection symptoms, not UTI symptoms, as the primary infection-related concern.