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

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, 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

Abstract

Objective: To evaluate the 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 β-hydroxybutyrate (BHB), and percentage of patients with BHB >0.6 and >1.5 mmol/L. The patients were administered placebo, sotagliflozin 200 mg, or sotagliflozin 400 mg once daily.

Results: A total of 191 ketosis-related AEs were reported, and 98 underwent adjudication. Of these, 37 events (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, respectively. No patient died of 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). Of sotagliflozin-treated patients, approximately 47% and 7% had ≥1 BHB measurement >0.6 mmol/L and >1.5 mmol/L, respectively (vs. 20% and 2%, respectively, of placebo-treated patients). Subsequent to the implementation of a risk mitigation plan, annualized DKA incidence was lower versus preimplementation in both the sotagliflozin 200 and 400 mg groups.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT02384941 NCT02421510.

© 2020 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Cumulative incidence of patients who had a BHB >0.6 mmol/L (A) and >1.5 mmol/L (B) over 52 weeks of treatment. SOTA, sotagliflozin.

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Source: PubMed

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