Sodium‐glucose co‐transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol

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.

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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

10.2337/figshare.12824342.v1 ◽

2020 ◽

Author(s):

Anne L. Peters ◽

Darren K. McGuire ◽

Thomas Danne ◽

Jake A. Kushner ◽

Helena W. Rodbard ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Ketoacidosis ◽

Risk Mitigation ◽

Pooled Analysis ◽

Once Daily ◽

Adjusted Incidence Rate ◽

Beta Hydroxybutyrate ◽

Design And Methods ◽

Adjusted Incidence

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.

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Predictors of diabetic ketoacidosis hospitalizations and hemoglobin A1c among youth with Type 1 diabetes.

Health Psychology ◽

10.1037/hea0000719 ◽

2019 ◽

Vol 38 (7) ◽

pp. 577-585 ◽

Cited By ~ 4

Author(s):

Katherine Semenkovich ◽

Kristoffer S. Berlin ◽

Rachel L. Ankney ◽

Kimberly L. Klages ◽

Mary E. Keenan ◽

...

Keyword(s):

Type 1 Diabetes ◽

Diabetic Ketoacidosis ◽

Hemoglobin A1c

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