BACKGROUND: In most patients with type 1 diabetes, adequate glycemic control is 
not achieved with insulin therapy alone. We evaluated the safety and efficacy of 
sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in 
combination with insulin treatment in patients with type 1 diabetes.
METHODS: In this phase 3, double-blind trial, which was conducted at 133 centers 
worldwide, we randomly assigned 1402 patients with type 1 diabetes who were 
receiving treatment with any insulin therapy (pump or injections) to receive 
sotagliflozin (400 mg per day) or placebo for 24 weeks. The primary end point 
was a glycated hemoglobin level lower than 7.0% at week 24, with no episodes of 
severe hypoglycemia or diabetic ketoacidosis after randomization. Secondary end 
points included the change from baseline in glycated hemoglobin level, weight, 
systolic blood pressure, and mean daily bolus dose of insulin.
RESULTS: A significantly larger proportion of patients in the sotagliflozin 
group than in the placebo group achieved the primary end point (200 of 699 
patients [28.6%] vs. 107 of 703 [15.2%], P<0.001). The least-squares mean change 
from baseline was significantly greater in the sotagliflozin group than in the 
placebo group for glycated hemoglobin (difference, -0.46 percentage points), 
weight (-2.98 kg), systolic blood pressure (-3.5 mm Hg), and mean daily bolus 
dose of insulin (-2.8 units per day) (P≤0.002 for all comparisons). The rate of 
severe hypoglycemia was similar in the sotagliflozin group and the placebo group 
(3.0% [21 patients] and 2.4% [17], respectively). The rate of documented 
hypoglycemia with a blood glucose level of 55 mg per deciliter (3.1 mmol per 
liter) or below was significantly lower in the sotagliflozin group than in the 
placebo group. The rate of diabetic ketoacidosis was higher in the sotagliflozin 
group than in the placebo group (3.0% [21 patients] and 0.6% [4], respectively).
CONCLUSIONS: Among patients with type 1 diabetes who were receiving insulin, the 
proportion of patients who achieved a glycated hemoglobin level lower than 7.0% 
with no severe hypoglycemia or diabetic ketoacidosis was larger in the group 
that received sotagliflozin than in the placebo group. However, the rate of 
diabetic ketoacidosis was higher in the sotagliflozin group. (Funded by Lexicon 
Pharmaceuticals; inTandem3 ClinicalTrials.gov number, NCT02531035 .).