Do SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors increase the risk of urinary tract infections in patients with good blood sugar control?

SGLT2 Inhibitors and Urinary Tract Infection Risk in Well-Controlled Diabetes

SGLT2 inhibitors do not increase the risk of urinary tract infections in patients with good blood sugar control or any level of glycemic control, based on large randomized controlled trials showing no difference in UTI rates compared to placebo. 1

Evidence from Major Clinical Trials

The highest quality evidence comes from landmark cardiovascular and renal outcome trials that collectively enrolled millions of patient-years:

• The 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 theoretical concerns about glycosuria creating a favorable bacterial growth environment 1

• A 2022 propensity score-matched population-based cohort study using UK and Canadian databases found SGLT2 inhibitors were not associated with higher UTI risk 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 receptor agonists (HR 0.81,95% CI 0.61-1.09), or thiazolidinediones (HR 0.81,95% CI 0.55-1.19) 2

• A 2024 cross-sectional study of 328 consecutive patients found no statistical difference in UTI presence between patients taking SGLT2 inhibitors versus other glucose-lowering medications 3

Contrast with Genital Mycotic Infections

The primary genitourinary concern with SGLT2 inhibitors is genital mycotic infections, not urinary tract infections:

• Genital mycotic infections occur in approximately 6% of SGLT2 inhibitor users versus 1% on placebo 1, 4
• These infections are typically mild, respond to brief antifungal courses, and rarely recur 1
• Most genital mycotic infections can be treated with standard antifungal therapy without discontinuing the SGLT2 inhibitor 4, 5

Impact of Glycemic Control

Good blood sugar control does not eliminate the already-low UTI risk with SGLT2 inhibitors, but poor glycemic control is an independent risk factor for UTIs:

• Higher HbA1c levels are associated with increased UTI predisposition regardless of SGLT2 inhibitor use 3
• In diabetic patients taking placebo, the odds for urinary tract infections were significantly increased compared to non-diabetic patients, suggesting diabetes itself—not SGLT2 inhibitors—drives UTI risk 6
• The 2024 study found that among SGLT2 inhibitor users, higher HbA1c predicted UTI likelihood, not the medication itself 3

Risk Factors That Actually Matter for UTIs

When UTIs do occur in SGLT2 inhibitor users, the following factors are responsible rather than the medication:

• Female gender is consistently associated with increased UTI likelihood 3
• Older age is associated with increased UTI susceptibility 7
• History of recurrent UTIs warrants cautious use 7, 5
• Higher BMI increases UTI predisposition 3
• Longer duration of type 2 diabetes is a predisposing factor 3

Clinical Management Algorithm

For patients without recurrent UTI history:

• Initiate SGLT2 inhibitors without additional UTI-specific precautions 7
• Counsel on proper genital hygiene to prevent mycotic infections 4, 5
• Continue SGLT2 inhibitor therapy during treatment of mild to moderate genital infections 4, 5

For patients with recurrent or severe UTI history:

• Use SGLT2 inhibitors cautiously, as cardiovascular and renal benefits may still outweigh risks 7, 5
• Implement preventive strategies and close monitoring 5
• Consider temporary discontinuation only in severe or recurrent UTIs 4, 5

For all patients:

• Monitor for symptoms of genitourinary infections during routine follow-up 4, 5
• Discontinue SGLT2 inhibitors immediately only for severe infections or Fournier's gangrene 4, 5
• Consider withholding during periods of acute illness, prolonged fasting, or surgery 1, 4

Common Pitfalls to Avoid

• Do not confuse the well-documented increase in genital mycotic infections with UTI risk—these are distinct entities with different management 4
• Do not discontinue SGLT2 inhibitors for mild genital infections—standard antifungal therapy is sufficient 4, 5
• Do not attribute UTIs to SGLT2 inhibitors when poor glycemic control or other risk factors are present—these are the actual culprits 3
• Do not overlook the rare but serious risk of Fournier's gangrene, which requires immediate discontinuation and urgent medical attention 1, 4

Special Populations

• Immunocompromised patients, including kidney transplant recipients, may require more careful monitoring for infections 4
• For patients with chronic kidney disease, SGLT2 inhibitor benefits on kidney and cardiovascular outcomes generally outweigh the risk of genitourinary infections 1, 5
• The reversible eGFR decline of 3-5 mL/min/1.73 m² in the first 4 weeks does not necessitate discontinuation 1