Garg SK, et al. - The goal of the study described in this paper was to assess the safety and effectiveness of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes. Among adult patients with type 1 diabetes who were receiving insulin therapy, the proportion of patients who achieved a glycated hemoglobin level lower than 7.0% and had no severe hypoglycemia or diabetic ketoacidosis was larger in the group that received sotagliflozin than in the placebo group. However, the rates of diabetic ketoacidosis and severe hypoglycemia were higher among patients who received sotagliflozin but did not achieve the target glycated hemoglobin level than among those who received placebo.

Methods

• For this study, they designed a phase 3, double-blind trial.
• This study was conducted at 133 centers worldwide.
• They randomly assigned total 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 endpoint was a glycated hemoglobin level lower than 7.0% at week 24, with no episodes of severe hypoglycemia or diabetic ketoacidosis after randomization.
• Secondary endpoints incorporated the change from baseline in glycated hemoglobin level, weight, systolic blood pressure, and mean daily bolus dose of insulin.

Results

• In this study, they observed that a major 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.
• They noted that 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).