Objective: Using a nationwide claim-based database in Japan, we investigated the reality of diabetic ketoacidosis (DKA) in patients with type 2 diabetes (T2D) treated with sodium-glucose cotransporter 2 (SGLT2) inhibitors.

Research Design and Methods: We identified initiators of SGLT2 inhibitors in the claims data from April 2014 to June 2019, and investigated the incidence of DKA in patients with T2D. Moreover, in multivariable-adjusted Cox proportional hazard models, hazard ratio (HR) was calculated using age, sex, body mass index (BMI) and the use of continuous subcutaneous insulin infusion (herein referred to as insulin pumps). Furthermore, regarding DKA events as the objective variable, receiver operating characteristic (ROC) analysis was conducted to calculate a cut-off value for the periods from the initiation of the SGLT2 inhibitors.

Results: During the observation period, among 173,025 initiators of SGLT2 inhibitors, patients with a diagnosis of DKA were 1,848 (1.1%), and those requiring inpatient treatment were 247 (0.14%). Factors associated with the diagnosis of DKA were 60- < 70years of age (HR, 1.59), BMI < 25kg/m2 (HR, 1.22) and the use of insulin pumps (HR, 4.61). Moreover, Factors associated with DKA requiring inpatient treatment were 60-70 years of age (HR, 2.64) and BMI < 25kg/m2 (HR, 1.31). As for the DKA events, ROC analysis revealed that the cut-off value was 60 days from the initiation of the SGLT2 inhibitors.

Conclusions: This survey revealed that the risk of DKA calculated using real-world database was particularly pronounced among 60- < 70years of age and BMI < 25kg/m2 patients. Furthermore, it became clear that special attention should be paid to the onset of DKA for about 60 days from the initiation of the SGLT2 inhibitors. This information would provide guidance to avoid DKA with SGLT2 inhibitors and optimize the treatment of T2D, especially in Asian descent.


T. Horii: None. Y. Oikawa: None. T. Higashiyama: None. K. Atsuda: None. A. Shimada: Advisory Panel; Self; Astellas Pharma Inc. Speaker’s Bureau; Self; Eli Lilly Japan K.K., Novo Nordisk Inc., Sanofi-Aventis.

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