HbA and Hypoglycemia Reductions at 24 and 52 Weeks With Sotagliflozin in Combination With Insulin in Adults With Type 1 Diabetes: The European inTandem2 Study.

Objective: The objective of this study was to evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 and 2 inhibitor sotagliflozin compared with placebo when combined with optimized insulin in adults with type 1 diabetes (T1D).

Research Design And Methods: In a double-blind, 52-week, international phase 3 trial, adults with T1D were randomized to placebo ( = 258) or once-daily oral sotagliflozin 200 mg ( = 261) or 400 mg ( = 263) after 6 weeks of insulin optimization. The primary outcome was change in HbA from baseline to 24 weeks. The first secondary end point was a composite of the proportion of patients with HbA <7.0%, no episode of severe hypoglycemia, and no episode of diabetic ketoacidosis (DKA) at week 24. Fasting glucose, weight, insulin dose, and safety end points were assessed through 52 weeks.

Results: At 24 weeks, placebo-adjusted changes in HbA from baseline (7.8%) were -0.37% and -0.35% with sotagliflozin 200 and 400 mg, respectively ( < 0.001), and differences were maintained at 52 weeks. At 52 weeks, greater proportions of sotagliflozin-treated patients (200 mg: 25.67%; 400 mg: 26.62%) than placebo-treated patients (14.34%; ≤ 0.001) met the composite end point, and sotagliflozin 400 mg reduced fasting plasma glucose (-0.87 mmol/L; = 0.008), weight (-2.92 kg; < 0.001), and total daily insulin dose (-8.2%; = 0.001). In a 24-week continuous glucose monitoring (CGM) substudy, postprandial glucose decreased ( ≤ 0.009) and CGM demonstrated up to 3 h more time in the target range of 3.9-10.0 mmol/L with sotagliflozin. Treatment satisfaction increased and diabetes distress decreased with sotagliflozin ( < 0.05 vs. placebo). The frequency of documented hypoglycemia was lower with sotagliflozin, and severe hypoglycemia occurred by week 52 in 13 patients (5.0%), 13 patients (5.0%), and 6 patients (2.3%) treated with placebo and sotagliflozin 200 and 400 mg, respectively. DKA occurred in 0 of 258 patients, 6 of 261 patients (2.3%), and 9 of 263 patients (3.4%) in these respective groups.

Conclusions: In a 1-year study, sotagliflozin was associated with statistically significant HbA reductions. More episodes of DKA and fewer episodes of documented and severe hypoglycemia were observed in patients using sotagliflozin relative to those receiving placebo (ClinicalTrials.gov, NCT02421510).