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

OBJECTIVEEvaluate 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).RESEARCH DESIGN AND METHODSThe inTandem1 trial, a double-blind, 52-week phase 3 trial, randomized North American adults with T1D to placebo (n = 268), sotagliflozin 200 mg (n = 263), or sotagliflozin 400 mg (n = 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.RESULTSFrom 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 P < 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 (P 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 P < 0.001). Diabetes Treatment Satisfaction Questionnaire scores increased significantly by 2.5 points with sotagliflozin versus placebo (P < 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.CONCLUSIONSIn 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).