TY - JOUR
T1 - Diabetic ketoacidosis and related events with sotagliflozin added to insulin in adults with type 1 diabetes
T2 - A pooled analysis of the intandem 1 and 2 studies
AU - Peters, Anne L.
AU - McGuire, Darren K.
AU - Danne, Thomas
AU - Kushner, Jake A.
AU - Rodbard, Helena W.
AU - Dhatariya, Ketan
AU - Sawhney, Sangeeta
AU - Banks, Phillip
AU - Jiang, Wenjun
AU - Davies, Michael J.
AU - Lapuerta, Pablo
N1 - Publisher Copyright:
© 2020 by the American Diabetes Association.
PY - 2020
Y1 - 2020
N2 - 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 b-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, suggest-ing that this risk can be managed with patient education.
AB - 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 b-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, suggest-ing that this risk can be managed with patient education.
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U2 - 10.2337/dc20-0924
DO - 10.2337/dc20-0924
M3 - Article
C2 - 32928957
AN - SCOPUS:85093829410
SN - 0149-5992
VL - 43
SP - 2713
EP - 2720
JO - Diabetes care
JF - Diabetes care
IS - 11
ER -