<b>Objective: </b>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.
<p><b>Research Design and Methods: </b>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. </p>
<p><b>Results:</b> 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. </p>
<p><b>Conclusion:</b> 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.</p>
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