SGLT2 Inhibitors Cause Glycosuria and Recurrent UTIs
SGLT2 inhibitors (sodium-glucose cotransporter-2 inhibitors) are the oral hypoglycemic agents that cause glycosuria and increase the risk of recurrent urinary tract infections. These drugs work by blocking glucose reabsorption in the renal proximal tubules, deliberately inducing urinary glucose excretion to lower blood glucose levels 1.
Mechanism of Action and UTI Risk
SGLT2 inhibitors reduce blood glucose by inhibiting renal tubular SGLT2, which is responsible for glucose reabsorption from urine, thereby reducing the renal glucose threshold and promoting urinary glucose excretion 1. This therapeutic glycosuria creates a glucose-rich urinary environment that promotes bacterial and fungal growth 2.
The most commonly implicated SGLT2 inhibitors include:
Clinical Evidence for UTI Risk
Genitourinary Tract Infections
Common adverse effects of SGLT2 inhibitors are genitourinary tract infections 1. The 2025 American Diabetes Association guidelines specifically note that SGLT2 inhibitors cause a higher rate of genital mycotic infections, especially in women, and are associated with a small increase in urinary tract infections 1.
Caution should be used in people with recurrent or severe urinary tract infections 1. The FDA drug label for empagliflozin (JARDIANCE) explicitly warns that treatment with SGLT2 inhibitors increases the risk for urinary tract infections and advises to evaluate patients for signs and symptoms of urinary tract infections and treat promptly if indicated 5.
Serious Complications
Postmarketing reports have documented serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors 5, 6. The canagliflozin (INVOKANA) FDA label specifically warns about urosepsis and pyelonephritis 6.
Research Data on UTI Incidence
A systematic review found an increased chance of UTI in SGLT2 inhibitor groups compared to control groups on placebo or other oral antidiabetic agents, with this increased risk found predominantly with dapagliflozin, canagliflozin, and tofogliflozin, regardless of dosing 7.
In clinical trials:
- Canagliflozin was associated with small increases in UTI incidence compared to control, though serious events or those leading to discontinuation were not increased 4
- Dapagliflozin showed a UTI prevalence of 5.3% in diabetic patients, with women more affected (76.2%) than men 3
- Animal studies demonstrated that persistent increases in urine glucose concentration directly correlated with increased susceptibility to UTI 2
High-Risk Populations
SGLT2 inhibitors should be used with particular caution in:
- Patients with a history of recurrent UTIs 1
- Women (higher risk of genital mycotic infections) 1
- Patients with bladder outlet obstruction or urinary stasis 8
- Older adults who are frail or prone to orthostasis 1
A case report documented E. coli septicemia in a patient with incomplete bladder emptying and urinary stasis after starting dapagliflozin, suggesting increased risk in patients with bladder outlet obstruction 8.
Clinical Management Recommendations
Before initiating SGLT2 inhibitors:
- Assess for history of recurrent or severe UTIs 1
- Query symptoms of urinary incontinence 1
- Evaluate for bladder outlet obstruction in appropriate patients 8
During treatment:
- Monitor for signs and symptoms of UTI and treat promptly if indicated 5, 6
- Consider discontinuation if recurrent UTIs become burdensome 1
- Symptoms of urinary incontinence should be queried after SGLT2 inhibitor initiation 1
Important Caveats
Despite the increased UTI risk, SGLT2 inhibitors provide significant cardiovascular and renal benefits, reducing the risk of major cardiovascular adverse events, renal events, and hospitalization rates for heart failure 1. The 2019 ESC guidelines note that in the CREDENCE trial, canagliflozin reduced the relative risk of the primary renal outcome by 30% compared with placebo 1.
The UTIs associated with SGLT2 inhibitors are typically mild to moderate and easily treated, with none causing treatment discontinuation in one study 3. However, the potential for serious complications like urosepsis and pyelonephritis requires vigilant monitoring 5, 6.