Danne T, et al. - In a double-blind, 52-week, international phase 3 trial, the researchers tested the efficacy and safety of the dual SGLT1 and SGLT2 inhibitor sotagliflozin compared with placebo when combined with optimized insulin in adults with type 1 diabetes (T1D). They found that sotagliflozin was correlated with statistically significant HbA_1c reductions in a 1-year study. In patients using sotagliflozin relative to those receiving placebo, more episodes of diabetic ketoacidosis (DKA) and fewer episodes of documented and severe hypoglycemia were observed.

Methods

• For the purpose of this investigation, adults with T1D were randomized to placebo (n= 258) or once-daily oral sotagliflozin 200 mg (n = 261) or 400 mg (n = 263) after 6 weeks of insulin optimization.
• Change in HbA_1c from baseline to 24 weeks was the primary outcome.
• A composite of the proportion of patients with HbA_1c <7.0%, no episode of severe hypoglycemia, and no episode of diabetic ketoacidosis (DKA) at week 24 were the first secondary end point.
• Through 52 weeks, fasting glucose, weight, insulin dose, and safety end points were evaluated.

Results

• The study results showed that placebo-adjusted changes in HbA_1c from baseline (7.8%) were -0.37% and -0.35% with sotagliflozin 200 and 400 mg, respectively (P < 0.001) at 24 weeks, and differences were maintained at 52 weeks.
• It was observed that greater proportions of sotagliflozin-treated patients (200 mg: 25.67%; 400 mg: 26.62%) than placebo-treated patients (14.34%; P ≤ 0.001) met the composite end point, and sotagliflozin 400 mg reduced fasting plasma glucose (-0.87 mmol/L; P=0.008), weight (-2.92 kg; P < 0.001), and total daily insulin dose (-8.2%; P=0.001) at 52 weeks.
• Postprandial glucose decreased (P ≤ 0.009), and CGM showed up to 3 h more time in the target range of 3.9–10.0 mmol/L with sotagliflozin in a 24-week continuous glucose monitoring (CGM) substudy.
• It was noted that treatment satisfaction increased and diabetes distress decreased with sotagliflozin (P < 0.05 vs placebo).
• Findings revealed that the frequency of documented hypoglycemia was lower with sotagliflozin, and severe hypoglycemia occurred by week 52 in 13 patients (5.0%), 13 patients (5.0%), and 6 patients (2.3%) treated with placebo and sotagliflozin 200 and 400 mg, respectively.
• According to the findings obtained, DKA occurred in 0 of 258 patients, 6 of 261 patients (2.3%), and 9 of 263 patients (3.4%) in these respective groups.