- The first dual sodium glucose cotransporter-1/-2 inhibitor sotagliflozin combined with optimized insulin therapy in a 1-year type 1 diabetes (T1D) study demonstrated sustained HbA1c reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, and improved patient-reported outcomes, but more slightly diabetic ketoacidosis, relative to placebo.
Why this matters
- "More than 1.25 million adults in the US live with T1D, and more than 75% of these people who use insulin alone have blood glucose levels above target," said lead study investigator John Buse, MD, PhD. Moreover, Dr. Buse emphasized, "The profile of sotagliflozin to improve glucose control beyond what can be achieved with intensified insulin alone while addressing these challenges has the potential to improve the lives of people with T1D."
- InTandem1 double-blind, 52-week, phase 3 trial of North American adults with T1D, randomly assigned to placebo (n=268), sotagliflozin 200 mg (n=263), or sotagliflozin 400 mg (n=262) after 6 weeks of insulin optimization.
- Primary endpoint was HbA1c change from baseline at 24 weeks and HbA1c, weight, and safety assessed through 52 weeks.
- Placebo-adjusted mean level 7.57% HbA1c was reduced by 0.36% and 0.41% with sotagliflozin 200 and 400 mg, respectively, by 24 weeks and 0.25% and 0.31%, respectively, by 52 weeks (all P<.001 class="">
- By 52 weeks, mean treatment differences between sotagliflozin 400 mg and placebo were −1.08 mmol/L for fasting plasma glucose, −4.32 kg for weight, −15.63% for bolus insulin dose, and −11.87% for basal insulin dose (all P<.001 class="">
- Diabetic ketoacidosis occurred in 9 (3.4%) and 11 (4.2%) patients receiving sotagliflozin 200 and 400 mg, respectively, and in 1 (0.4%) receiving placebo. Severe hypoglycemia occurred in 17 (6.5%) patients from each sotagliflozin group and 26 (9.7%) patients receiving placebo.
- Long-term effects of sotagliflozin remain to be determined.
- Data on glycated hemoglobin levels were masked to investigators after screening to make the trial consistent with other trials of sotagliflozin. If investigators had had access to the data, they may have adjusted insulin therapy more aggressively to more effectively meet target glycated hemoglobin levels.