DKA risk is almost tripled with SGLT-2 inhibitors

  • Douros A & al.
  • Ann Intern Med
  • 28 Jul 2020

  • curated by Miriam Tucker
  • Clinical Essentials
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Takeaway

  • Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are associated with an almost tripled risk for diabetic ketoacidosis (DKA) compared with dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with type 2 diabetes (T2D).
  • The association appears to reflect a class effect.

Why this matters

  • SGLT-2i use is increasing because of beneficial cardiovascular and renal effects.

Study design

  • From UK and Canadian electronic health care databases: 208,757 new SGLT-2i users matched to 208,757 new DPP-4i users during 2013-2018.  
  • Specific SGLT-2is used were 42.3% canagliflozin, 30.7% dapagliflozin, 27.0% empagliflozin.
  • Funding: Canadian Institutes of Health Research; others.

Key results

  • During mean 0.9 years, 521 were hospitalized with DKA (1.41 per 1000 person-years).
  • DKA incidence rates (per 1000 person-years): 
    • 2.03 for SGLT-2i vs 0.75 DPP-4i.
    • Adjusted HR: 2.85 (95% CI, 1.99-4.08).
  • Per individual SGLT-2i, incidence rates were (95% CIs):
    • Dapagliflozin: 1.86 (1.11-3.10);
    • Empagliflozin: 2.52 (1.23-5.14); and 
    • Canagliflozin: 3.58 (2.13-6.03).
  • SGLT-2i-associated DKA incidence rate was higher in those with vs without prior insulin use (3.52 vs 1.43).
  • No difference by age, sex, or recipient type; results were consistent in sensitivity analyses.

Limitations

  • Observational, possible residual confounding.
  • No data on HbA1c and patient adherence.  
  • Sites differed in individual SGLT-2i use.
  • Short follow-up.