Would stopping dapagliflozin (a SGLT2 inhibitor) be beneficial in managing a patient with type 2 diabetes and recurrent urinary tract infections (UTIs), including a recent episode of urosepsis?

Should Dapagliflozin Be Stopped in a Patient with Recurrent UTIs and Recent Urosepsis?

No, dapagliflozin should generally be continued for its critical cardiovascular and renal protective benefits, but temporarily withheld during acute illness and restarted once the patient is clinically stable with resumed oral intake. 1, 2

Evidence on UTI Risk with Dapagliflozin

The concern about stopping dapagliflozin stems from theoretical increased UTI risk due to glucosuria, but the actual clinical data is reassuring:

• Large randomized controlled trials showed no difference in rates of serious urinary tract infections or urosepsis between SGLT2 inhibitors and placebo, despite postmarketing reports of rare cases requiring hospitalization 3
• Pooled safety data from 12 trials (3,152 dapagliflozin patients vs 1,393 placebo) demonstrated UTI rates of only 4.3-5.7% with dapagliflozin versus 3.7% with placebo—a minimal absolute increase 4
• A 2022 study found UTI prevalence of only 5.3% in patients on dapagliflozin, with infections being mild-to-moderate and easily treated without requiring drug discontinuation 5
• Most importantly, discontinuations due to UTI were rare: only 0.3% of dapagliflozin-treated patients versus 0.1% placebo 4

Critical Cardiovascular and Renal Benefits That Would Be Lost

Permanently stopping dapagliflozin would sacrifice substantial mortality and morbidity benefits:

• 39% reduction in kidney disease progression (sustained eGFR decline ≥50%, ESKD, or renal/cardiovascular death) 3, 1
• 44% reduction in kidney-specific outcomes (sustained eGFR decline, ESKD, or renal death) 3, 1
• 29% reduction in cardiovascular death or heart failure hospitalization 3, 1
• 31% reduction in all-cause mortality 1

These benefits persist even at lower eGFR levels (≥20 mL/min/1.73 m²) and are independent of glycemic control 3, 1

Proper Management Algorithm

During Acute Illness (Current Urosepsis Episode):

1. Temporarily discontinue dapagliflozin during hospitalization for urosepsis, as recommended for any acute illness with reduced oral intake 1, 2
2. Treat the infection aggressively with appropriate antibiotics 2
3. Assess and correct volume depletion before restarting 1, 2
4. Monitor for signs of ketoacidosis (even with normal glucose levels) 2

After Recovery:

1. Resume dapagliflozin 10 mg daily once the patient is clinically stable and has resumed normal oral intake 1, 2
2. The cardiovascular and renal protective benefits far outweigh the minimal UTI risk 3

Long-Term Prevention Strategy:

• Educate the patient on sick day rules: hold dapagliflozin during any acute illness with fever, vomiting, diarrhea, or reduced oral intake 1
• Counsel on daily hygiene measures to reduce genital mycotic infection risk 1
• Instruct to seek immediate medical attention for signs of serious infection 2
• Consider evaluating for underlying urologic abnormalities (bladder outlet obstruction, incomplete emptying) that may predispose to recurrent UTIs 6

Special Considerations for This Patient

The FDA label specifically warns about urosepsis and pyelonephritis requiring hospitalization with SGLT2 inhibitors, but emphasizes evaluating and treating infections promptly rather than discontinuing the drug permanently 2. The 2018 ACC guidelines note that while spontaneous postmarketing reports exist, large clinical trials showed no difference in serious UTI rates 3.

Key Distinction:

• Temporary withholding during acute illness: Appropriate and recommended 1, 2
• Permanent discontinuation: Not justified based on current evidence, given the substantial mortality benefit and lack of increased serious UTI risk in trials 3

Common Pitfall to Avoid

Do not permanently discontinue dapagliflozin solely because of recurrent UTIs or a single episode of urosepsis. 3, 1 The evidence shows that UTIs with dapagliflozin are generally mild-to-moderate, respond to standard antibiotics, and rarely require drug discontinuation 4, 5. The substantial cardiovascular and renal protective benefits—including a 31% mortality reduction—should not be sacrificed for a theoretical risk that has not materialized in large randomized trials 3, 1.

If UTIs continue to recur after restarting dapagliflozin, investigate other predisposing factors such as bladder dysfunction, incomplete emptying, or structural abnormalities before attributing causality to the medication 6, 7.