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