Diabetic Ketoacidosis and Severe Hypoglycemia Risks with Ipragliflozin/Insulin Versus Insulin in Type 1 Diabetes: A Japanese Real-World Database Study

Diabetes Ther. 2025 Nov 18. doi: 10.1007/s13300-025-01815-7. Online ahead of print.

ABSTRACT

INTRODUCTION: Ipragliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor approved in Japan as an adjunct to insulin therapy for the management of type 1 diabetes (T1D). Diabetic ketoacidosis (DKA) and severe hypoglycemia (SH) have been specified as important identified risks for ipragliflozin; however, real-world data on the incidences of these events are limited. We compared the incidences of initial DKA and SH in patients with T1D newly treated with ipragliflozin in combination with insulin versus those treated with insulin.

METHODS: This post-marketing surveillance study used data from the JMDC Claims Database between June 2018 and December 2021. Using propensity score matching, patients with T1D were matched 1:10 to the ipragliflozin/insulin group and insulin group. For each treatment group, incidence rates (IRs) of DKA and SH were plotted on a Kaplan-Meier curve, and IRs per 1000 patient-years (PY) were calculated. The risks of DKA and SH were compared between the treatment groups by calculating the hazard ratios (HRs) and 95% confidence intervals (CIs) using a Cox proportional-hazards model.

RESULTS: The incidence of DKA was not significantly different between the ipragliflozin/insulin and the insulin groups (log-rank p = 0.793); the IRs of DKA were 8.3 and 8.5 per 1000 PY, respectively (HR 0.902, 95% CI 0.418‒1.945; p = 0.792). The incidence of SH was significantly lower in the ipragliflozin/insulin group versus the insulin group (log-rank p = 0.001). The IRs of SH per 1000 PY were 6.6 and 21.7, respectively (HR 0.284, 95% CI 0.126‒0.637; p = 0.002).

CONCLUSIONS: Ipragliflozin/insulin combination therapy showed no difference in the incidence of DKA, but a lower incidence of SH, versus insulin therapy in patients with T1D in Japan. These results suggest that ipragliflozin treatment is not associated with increased incidences of initial DKA or SH; however, its use should be accompanied by appropriate monitoring, education, and risk mitigation strategies to minimize the occurrence of these events.

PMID:41252111 | DOI:10.1007/s13300-025-01815-7