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

Analysis of data from two identical 52-week, RCTs found that in patients with type 1 diabetes, confirmed DKA incidence increased when sotagliflozin was added to insulin compared with insulin alone and a lower incidence was observed following enhanced risk mitigation plan.

SPS commentary:

In analysis, 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.

In April 2019, sotagliflozin, a dual SGLT1 and SGLT2 inhibitor was approved in EU (but not launched) as adjunct to insulin therapy in adults with type 1 diabetes and a body mass index ≥27 kg/m2, who could not achieve adequate glycaemic control despite optimal insulin therapy. A New Drug Application was however rejected by the FDA.

NICE guidance issued in Feb 2020 recommends sotagliflozin with insulin as an option for treating type 1 diabetes in adults with BMI of at least 27 kg/m2, when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy, only if:

  • sotagliflozin is given as one 200 mg tablet daily
  • they are on insulin doses of 0.5 units/kg of body weight/day or more and
  • they have completed a structured education programme that is evidence based, quality assured, delivered by trained educators and includes information about diabetic ketoacidosis, such as: how to recognise its risk factors, signs and symptoms, how and when to monitor blood ketone levels, what actions to take for elevated blood ketones and treatment is started and supervised by a consultant physician specialising in endocrinology and diabetes treatment, and HbA1c levels are assessed after 6 months and regularly after this.

Sotagliflozin is not yet available in the NHS, but the company anticipated that it will be available to the NHS within 12 months from publication of the guidance.

Diabetes Care

Resource links:

NICE TA 622