On‐label use of sodium–glucose cotransporter 2 inhibitors might increase the risk of diabetic ketoacidosis in patients with type 1 diabetes

AIMS/INTRODUCTION: This study aimed to investigate the risk of diabetic ketoacidosis (DKA) in insulin‐treated type 1 diabetes patients administered sodium–glucose cotransporter 2 (SGLT2) inhibitors in real‐world clinical practice. MATERIALS AND METHODS: We carried out a real‐world, retrospective, observational cohort study using Japanese Medical Data Vision, a diagnosis procedure combination database. We identified insulin‐treated adult type 1 diabetes patients enrolled from December 2018 to October 2019. We assessed the incidence and risk of DKA in type 1 diabetes patients using SGLT2 inhibitors in an ‘on‐label’ manner. Cox multivariate regression analyses were carried out to determine clinical factors linked to SGLT2 inhibitor‐associated DKA. RESULTS: Of 11,475 type 1 diabetes patients, 1,898 (16.5%) were prescribed SGLT2 inhibitors. DKA occurred in 139 (7.3%) of these patients, with 20.2 incidences per 100 person‐years. These patients also showed significantly higher DKA rates than did those not receiving SGLT2 inhibitors (hazard ratio 1.66, 95% confidence interval 1.33–2.06; P < 0.001). The mean time until DKA onset in SGLT2 inhibitor‐treated type 1 diabetes patients was 30.6 ± 30.1 days. The risk of SGLT2 inhibitor‐associated DKA increased in type 1 diabetes patients irrespective of sex, age or body mass index. However, the risk did not increase in type 1 diabetes patients receiving continuous subcutaneous insulin infusion, which warrants further investigation because of the small number of type 1 diabetes patients receiving continuous subcutaneous insulin infusion. CONCLUSIONS: ‘On‐label’ SGLT2 inhibitor use might increase DKA risk among insulin‐treated type 1 diabetes patients irrespective of sex, age or body mass index. Both type 1 diabetes patients and healthcare providers should be wary of DKA, especially during the first month of initiating SGLT2 inhibitors.