Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American inTandem1 Study.

Abstract

Evaluate the efficacy and safety of the dual sodium-glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor sotagliflozin in combination with optimized insulin in type 1 diabetes (T1D). The inTandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo (<i>n</i> = 268), sotagliflozin 200 mg (<i>n</i> = 263), or sotagliflozin 400 mg (<i>n</i> = 262) after 6 weeks of insulin optimization. The primary end point was HbA_1c change from baseline at 24 weeks. HbA_1c, weight, and safety were also assessed through 52 weeks. From a mean baseline of 7.57%, placebo-adjusted HbA_1c reductions were 0.36% and 0.41% with sotagliflozin 200 and 400 mg, respectively, at 24 weeks and 0.25% and 0.31% at 52 weeks (all <i>P</i> < 0.001). Among patients with a baseline HbA_1c ≥7.0%, an HbA_1c <7% was achieved by 15.7%, 27.2%, and 40.3% of patients receiving placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively (<i>P</i> ≤ 0.003 vs. placebo) at 24 weeks. At 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, and -15.63% for bolus insulin dose and -11.87% for basal insulin dose (all <i>P</i> < 0.001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points with sotagliflozin versus placebo (<i>P</i> < 0.001) at 24 weeks. Genital mycotic infections and diarrhea occurred more frequently with sotagliflozin. Adjudicated diabetic ketoacidosis (DKA) 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. In a 1-year T1D study, sotagliflozin combined with optimized insulin therapy was associated with sustained HbA_1c reduction, weight loss, lower insulin dose, fewer episodes of severe hypoglycemia, improved patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, NCT02384941).