Efficacy and safety of ipragliflozin add-on therapy to insulin in Japanese patients with type 1 diabetes mellitus: A randomized, double-blind, phase 3 trial.

AIM: To assess the efficacy and safety of once-daily 50-mg ipragliflozin versus placebo in Japanese patients with type 1 diabetes mellitus (T1DM) inadequately controlled with insulin.

MATERIALS AND METHODS: We conducted a multicenter, double-blind, parallel-group, placebo-controlled phase 3 study. Patients (N=175) were randomized (2:1) to receive once-daily 50-mg ipragliflozin (n=115) or placebo (n=60), combined with insulin, for 24 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c); key secondary endpoints included change in insulin dose and body weight. Treatment-emergent adverse events (TEAEs) were evaluated.

RESULTS: The ipragliflozin group demonstrated a significant decrease in HbA1c from baseline to end of treatment versus the placebo group: adjusted mean difference (AMD), -0.36% (95% CI; -0.57, -0.14) (-3.8 mmol/mol [-6.2, -1.5]); P=0.001. Significant reductions in total daily insulin dose (AMD: -7.35 IU [95% CI; -9.09, -5.61]; P<0.001) and body weight (AMD: -2.87 kg [95% CI; -3.58, -2.16]; P<0.001) were observed for the ipragliflozin group versus placebo. Two serious TEAEs occurred (major hypoglycemia and abdominal abscess); both were in the placebo group. All other TEAEs were mild or moderate in severity. Four cases of study discontinuation occurred; three in the placebo group and one in the ipragliflozin group. No diabetic ketoacidosis was reported for any patient in this study.

CONCLUSIONS: Daily 50-mg ipragliflozin in combination with insulin significantly reduced HbA1c, daily insulin dose, and body weight versus placebo in patients with T1DM. No safety concerns were identified after 24 weeks of treatment. Overall, once-daily 50-mg ipragliflozin was both efficacious and well tolerated. This article is protected by copyright. All rights reserved.