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Ann Intern Med. 2019 Jul 30. doi: 10.7326/M18-3136. [Epub ahead of print]

Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Severe Urinary Tract Infections: A Population-Based Cohort Study.

Author information

Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (C.V.D., S.S., D.K., M.F., A.T., E.P.).



Prior studies evaluating risk for severe urinary tract infections (UTIs) with sodium-glucose cotransporter-2 (SGLT-2) inhibitors have reported conflicting findings.


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.


Population-based cohort study.


2 large, U.S.-based databases of commercial claims (March 2013 to September 2015).


Within each database, 2 cohorts were created and matched 1:1 on propensity score. Patients were aged 18 years or older, had type 2 diabetes mellitus, and were initiating use of SGLT-2 inhibitors versus DPP-4 inhibitors (cohort 1) or GLP-1 agonists (cohort 2).


The primary outcome was a severe UTI event, defined as a hospitalization for primary UTI, sepsis with UTI, or pyelonephritis; the secondary outcome was outpatient UTI treated with antibiotics. Hazard ratios [HRs] were estimated in each propensity score-matched cohort, with adjustment for more than 90 baseline characteristics.


After 1:1 matching on propensity score, 123 752 patients were identified in cohort 1 and 111 978 in cohort 2 in the 2 databases. In cohort 1, persons newly receiving SGLT-2 inhibitors had 61 severe UTI events (incidence rate [IR] per 1000 person-years, 1.76), compared with 57 events in the DPP-4 inhibitor group (IR, 1.77) (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 [CI, 0.53 to 0.99]). Findings were robust across sensitivity analyses; within several subgroups of age, sex, and frailty; and for canagliflozin and dapagliflozin individually. In addition, SGLT-2 inhibitors were not associated with increased risk for outpatient UTIs (cohort 1: HR, 0.96 [CI, 0.89 to 1.04]; cohort 2: HR, 0.91 [CI, 0.84 to 0.99]).


Generalizability of the study findings may be limited to patients with commercial insurance.


In a large cohort of patients seen in routine clinical practice, risk for severe and nonsevere UTI events among those initiating SGLT-2 inhibitor therapy was similar to that among patients initiating treatment with other second-line antidiabetic medications.

Primary Funding Source:

Brigham and Women's Hospital, Division of Pharmacoepidemiology and Pharmacoeconomics.


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