R. Tamura, H. Kim, Y. Takumi, M. Ishihara, T. Kobayashi, D. Layton, et al. (2026). Incidence of Diabetic Ketoacidosis in Dapagliflozin-Treated Japanese Patients With Type 1 Diabetes Mellitus: An Observational Cohort Database Study. Pharmacoepidemiology and drug safety, 35(1), e70294. https://doi.org/10.1002/pds.70294

PubMed 41449745

[Abstract]
PURPOSE: Diabetic ketoacidosis (DKA) is an important identified risk of treatment with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin, particularly in patients with type 1 diabetes mellitus (T1DM). We evaluated the DKA incidence rate (IR) among dapagliflozin-treated Japanese patients with T1DM receiving concomitant insulin.

METHODS: This observational, cohort, post-marketing study utilized data from the JMDC Payer database. All patients had T1DM and were prescribed insulin; the dapagliflozin group included dapagliflozin-treated patients and the control group included SGLT2i nonusers. The study outcomes were DKA events (a composite of DKA resulting in hospitalization and/or death). Using a prevalent new-user design, time-stratified sequential propensity score (PS) matching was implemented.

RESULTS: Between March 2019 and March 2021, 5886 insulin-treated patients with T1DM were eligible, and 327/5886 patients newly received dapagliflozin. After up to 1:3 PS-matching, 327 dapagliflozin-treated patients and 980 matched controls were analyzed. The IRs (95% confidence interval) of DKA in the PS-matched cohort were 1.54 per 100 person-years (/100 PY; 0.42-3.95) and 1.14/100 PY (0.55-2.10) in the dapagliflozin and control groups, respectively, with a hazard ratio of 1.28 (0.40-4.09). The IRs in the unmatched cohort were 1.54/100 PY (0.42-3.95) and 0.97/100 PY (0.72-1.27) in the dapagliflozin and control groups, respectively.

CONCLUSION: DKA incidence in dapagliflozin-treated T1DM patients was slightly higher than in SGLT2i nonusers. As the confidence intervals overlapped, these results did not suggest any meaningful differences or unexpected higher risk of DKA, consistent with previous reports in other countries.