Sotagliflozin is a dual inhibitor of sodium–glucose cotransporter (SGLT2) 1 and 2 that is licensed as an adjunctive therapy to insulin in people with type 1 diabetes in the EU. This pooled analysis of data from two phase 3 clinical trials evaluated the incidence of diabetic ketoacidosis (DKA) in a total of 1575 people with type 1 diabetes who were randomised 1:1:1 to adjuctive sotagliflozin 200 mg, 400 mg or placebo for 1 year.
A total of 191 ketosis events were identified, occurring in 9.7%, 13.9% and 2.7% in the sotagliflozin 200 mg, 400 mg and placebo groups, respectively. Most of these were reversed by the participants or clinicians with usual measures, leaving 98 events to be submitted for adjudication as per the study protocols. Of these, 37 events in 36 participants were adjudicated to be DKA, with all but one occurring in the sotagliflozin groups. The DKA incidence rate was 3.1, 4.2 and 0.2 events per 100 person-years for sotagliflozin 200 mg, 400 mg and placebo, respectively.
Blood glucose at the time of DKA was ≥13.9 mmol/L in 64% of cases. Nineteen events were related to insulin pump failure and 14 to intercurrent illness. DKA risk was higher in people on insulin pump therapy, those with a BMI <27 kg/m2 (in whom sotagliflozin is not licensed in the EU) and those who had reductions in insulin dose of ≥10–20% compared with baseline. DKA risk was lower in the second part of the study, after warnings of increased risk of euglycaemic DKA in users of SGLT2 inhibitors were published.
Peters AL, McGuire DK, Danne T et al (2020) 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. Diabetes Care 43: 2713–20. https://doi.org/10.2337/dc20-0924