SGLT-2 Inhibitors Don’t Increase Risk of Severe UTI

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Sodium–glucose cotransporter-2 (SGLT-2) inhibitors are not associated with an increased risk of severe urinary tract infection (UTI) in routine clinical practice, concludes a study in Annals of Internal Medicine.

Using two large commercial claims databases based in the United States, the researchers created propensity-matched cohorts of adults with type 2 diabetes who were initiating treatment with SGLT-2 inhibitors versus other antidiabetic drugs. Cohort 1 included matched groups of 61,876 patients starting SGLT-2 inhibitors versus dipeptidyl peptidase-4 inhibitors. Cohort 2 included groups of 55,989 patients starting SGLT-2 inhibitors versus glucagon-like peptide-1 receptor agonists. Severe UTIs were defined as hospitalization

Sodium–glucose cotransporter-2 (SGLT-2) inhibitors are not associated with an increased risk of severe urinary tract infection (UTI) in routine clinical practice, concludes a study in Annals of Internal Medicine.

Using two large commercial claims databases based in the United States, the researchers created propensity-matched cohorts of adults with type 2 diabetes who were initiating treatment with SGLT-2 inhibitors versus other antidiabetic drugs. Cohort 1 included matched groups of 61,876 patients starting SGLT-2 inhibitors versus dipeptidyl peptidase-4 inhibitors. Cohort 2 included groups of 55,989 patients starting SGLT-2 inhibitors versus glucagon-like peptide-1 receptor agonists. Severe UTIs were defined as hospitalization for primary UTI, sepsis with UTI, or pyelonephritis. Outpatient UTI treated with antibiotics was evaluated as a secondary outcome.

In cohort 1, the incidence rate of severe UTIs (per 1000 person-years) was 1.77 in patients starting SGLT-2 inhibitors and 1.76 in those starting dipeptidyl peptidase-4 inhibitors. In cohort 2, the incidence rates were 2.15 with SGLT-2 inhibitors and 2.96 with glucagon-like peptide-1 receptor agonists.

There were no significant differences in sensitivity analyses including subgroups defined by age, sex, or frailty, or for canagliflozin versus dapagliflozin. There was also no increase in the risk of outpatient UTIs for patients starting SGLT-2 inhibitors.

Because SGLT-2 inhibitors increase glucose availability in the urinary tract, there is concern that they might increase the risk of genitourinary tract infections. Despite a U.S. Food and Drug Administration label warning, there is limited evidence on the association between these drugs and the risk of severe UTIs.

This large population-based study finds no increase in severe UTI events in patients with type 2 diabetes starting SGLT-2 inhibitor therapy, compared with other antidiabetic drugs. The researchers conclude, “[O]ther factors beyond risk for UTI events should be considered in decisions about whether to prescribe SGLT-2 therapy for patients with diabetes in routine care settings” [Dave CV, et al. Sodium–glucose cotransporter-2 inhibitors and the risk for severe urinary tract infections: A population-based cohort study. Ann Intern Med 2019; doi: 10.7326/M18-3136].

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