Effects of Sotagliflozin Combined with Intensive Insulin Therapy in Young Adults with Poorly Controlled Type 1 Diabetes: The JDRF Sotagliflozin Study.

BACKGROUND Young adults with type 1 diabetes (T1D) tend to have higher A1C than older adults and are at increased risk for diabetic ketoacidosis (DKA). Oral adjuncts to insulin have not been previously studied in this population. METHODS In this phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, adults aged 18-30 years with T1D and A1C ≥9.0% were randomly assigned to placebo (n=42) or sotagliflozin 400 mg (n=43) in addition to insulin for 12 weeks. Insulin doses were adjusted to meet glucose targets (preprandial 80-130 mg/dL, postprandial <180 mg/dL). The primary endpoint was change from baseline in A1C at Week 12. RESULTS From a baseline of 9.8%, mean A1C decreased by 1.0% with placebo and 1.3% with sotagliflozin ( 0.4% [95% confidence interval (CI) 0.8 to 0.1]; P=0.10 vs placebo). In the prespecified A1C ≤10.0% subgroup, the treatment difference was 0.8% ( 1.3 to 0.2; P=0.006), favoring sotagliflozin. Overall, relative to placebo, postprandial glucose (PPG) decreased by 56.6 mg/dL (-89.7 to -23.6; P<0.001) and weight by 2.37 kg ( 3.5 to 1.2; P<0.001). More patients achieved an A1C <7.0% with sotagliflozin (16.3%) than placebo (2.4%; P=0.026). Rates of documented hypoglycemia and severe hypoglycemia were similar between groups. One DKA event occurred with placebo and none with sotagliflozin. CONCLUSIONS In young adults with T1D and suboptimal glycemic control, sotagliflozin plus insulin for 12 weeks numerically improved A1C and significantly improved A1C goal attainment, PPG, and body weight. Sotagliflozin plus insulin was generally well tolerated without any episodes of DKA (NCT02383940).