Diabetic Ketoacidosis and Related Events With Sotagliflozin Added to Insulin in Adults With Type 1 Diabetes: A Pooled Analysis of the inTandem 1 and 2 Studies
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Research Design and Methods: Data from two identically designed, 52-week, randomized studies were pooled and analyzed for DKA, changes in beta-hydroxybutyrate (BHB), and percentage of patients with BHB >0.6 and >1.5 mmol/L; patients were administered placebo, sotagliflozin 200 mg, or sotagliflozin 400 mg once daily.
Results: A total of 191 ketosis-related AEs were reported; 98 underwent adjudication. Of these, 37 (36 patients) were adjudicated as DKA, with an exposure-adjusted incidence rate of 0.2, 3.1, and 4.2 events per 100 patient-years for placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg. No patient died from a DKA event. From a baseline BHB of ~0.13 mmol/L, sotagliflozin treatment led to a small median increase over 52 weeks (≤0.05 mmol/L at all time points). Approximately 47% and 7% of sotagliflozin-treated patients had ≥1 BHB measurement >0.6 mmol/L and >1.5 mmol/L (vs 20% and 2% of placebo-treated patients). Subsequent to the implementation of a risk mitigation plan, annualized DKA incidence was lower versus pre-implementation in both the sotagliflozin 200-mg and 400-mg groups.
Conclusion: In patients with type 1 diabetes, confirmed DKA incidence increased when sotagliflozin was added to insulin compared with insulin alone. A lower incidence of DKA was observed following the implementation of an enhanced risk mitigation plan, suggesting that this risk can be managed with patient education.