SGLT-2 inhibitors not associated with increased risk for severe UTIs

An accompanying editorial said that while the study's finding is reassuring, it should be considered with caution, especially since high-risk patients and those with previous urinary tract infections (UTIs) were excluded.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors do not seem to increase risk for severe urinary tract infections (UTIs) when compared to other second-line antidiabetic therapies, a study found.

Researchers studied two large, U.S.-based databases of commercial claims to assess whether patients initiating use of SGLT-2 inhibitors were at increased risk for severe UTI events compared with those initiating use of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 receptor (GLP-1) agonists. The primary outcome was a severe UTI event, defined as a hospitalization for primary UTI, sepsis with UTI, or pyelonephritis. Findings were published July 30 by Annals of Internal Medicine.

The study included two propensity-matched cohorts of patients (123,752 patients in cohort 1 and 111,978 in cohort 2), and in both, UTI event rates were similar in those using SGLT-2 inhibitors versus other antidiabetic medications. In cohort 1, persons newly receiving SGLT-2 inhibitors had 61 severe UTI events (incidence rate [IR] per 1,000 person-years, 1.76), compared with 57 events in the DPP-4 inhibitor group (IR, 1.77) (hazard ratio [HR], 0.98; 95% CI, 0.68 to 1.41). In cohort 2, those receiving SGLT-2 inhibitors had 73 events (IR, 2.15), compared with 87 events in the GLP-1 agonist group (IR, 2.96) (HR, 0.72; 95% CI, 0.53 to 0.99). SGLT-2 inhibitors were also not associated with any increase in the study's secondary outcome of outpatient UTIs treated with antibiotics (HRs, 0.96 [95% CI, 0.89 to 1.04] in cohort 1 and 0.91 [95% CI, 0.84 to 0.99] in cohort 2).

According to the researchers, these findings suggest that other factors beyond risk for UTI should be considered in decisions about whether to prescribe SGLT-2 inhibitor therapy for patients with diabetes in routine care settings.

The authors of an accompanying editorial said that the study results are reassuring but should be considered with some caution. First, the study excluded high-risk patients and those with a history of UTIs. Second, some analyses of secondary outcomes such as urosepsis had more modest statistical power in some comparisons, suggesting further safety assessments may be needed to address these issues.

“Ultimately, although some uncertainty remains, [this study] provides encouraging evidence of the real-world safety of SGLT-2 inhibitors, allowing patients to benefit from their use with greater confidence in their safety with respect to severe UTI,” the editorial stated.