American Diabetes Association
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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

posted on 2020-09-14, 15:57 authored by Anne L. Peters, Darren K. McGuire, Thomas Danne, Jake A. Kushner, Helena W. Rodbard, Ketan Dhatariya, Sangeeta Sawhney, Phillip Banks, Wenjun Jiang, Michael J. Davies, Pablo Lapuerta
Objective: To evaluate incidence and risk factors for diabetic ketoacidosis (DKA) and related adverse events (AEs) in adults with type 1 diabetes treated with sotagliflozin adjunctive to insulin.

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.


This study was sponsored and conducted by Lexicon Pharmaceuticals, Inc.


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