OBJECTIVE: 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).
RESEARCH DESIGN AND METHODS: The 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 HbA1c change from baseline at 
24 weeks. HbA1c, weight, and safety were also assessed through 52 weeks.
RESULTS: From a mean baseline of 7.57%, placebo-adjusted HbA1c 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 
HbA1c ≥7.0%, an HbA1c <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.
CONCLUSIONS: In a 1-year T1D study, sotagliflozin combined with optimized 
insulin therapy was associated with sustained HbA1c reduction, weight loss, 
lower insulin dose, fewer episodes of severe hypoglycemia, improved 
patient-reported outcomes, and more DKA relative to placebo (ClinicalTrials.gov, 
NCT02384941).