SGLT-2 inhibitors are not linked to increased UTI risk

  • Dave CV & al.
  • Ann Intern Med
  • 30 Jul 2019

  • International Clinical Digest
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Takeaway

  • Sodium-glucose cotransporter-2 inhibitor (SGLT-2i) use does not seem to raise the risk for urinary tract infections (UTIs).  

Why this matters

  • The association between SGLT-2is and UTIs has been unclear.
  • All SGLT-2i labels carry an FDA warning about severe UTIs.

Study design

  • Study of 2 US claims databases of propensity-matched cohorts with type 2 diabetes (T2D) initiating new second-line agents:
    • Cohort 1: 123,752 SGLT-2is vs dipeptidyl peptidase-4 inhibitors (DPP-4is); and
    • Cohort 2: 111,978 SGLT-2is vs glucagon-like peptide-1 receptor agonists (GLP-1RAs).
  • Severe UTI: hospitalization for primary UTI, sepsis with UTI, or pyelonephritis.
  • Funding: Harvard Medical School.

Key results

  • Cohort 1: 61,876 matched pairs:
    • SGLT-2is:
      • 61 severe UTI events.
      • Incidence ratio (IR): 1.76 cases/1000 person-years. 
    • DPP-4is:
      • 57 severe events.
      • IR: 1.77/1000 person-years.
      • Adjusted HR, 0.98 (P=.93).
  • Cohort 2: 55,989 matched pairs: 
    • SGLT-2is:
      • 73 events.
      • IR: 2.15/1000 person-years. 
    • GLP-1RAs:
      • 87 events.
      • IR: 2.96/1000 person-years.
    • HR, 0.72 (P=.040).
  • SGLT-2is were not associated with increased risk for UTI hospitalizations (HRs; 95% CIs):
    • Cohort 1: 0.68 (0.54-0.87); 
    • Cohort 2: 0.78 (0.62-0.99). 
  • SGLT-2is were not associated with treated outpatient UTIs (HRs; 95% CIs):
    • Cohort 1: 0.96 (0.89-1.04); 
    • Cohort 2: 0.91 (0.84-0.99).

Limitations

  • Observational, not randomized.
  • All commercially insured population.
  • Excluded those at highest UTI risk.