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 ipragliflozin 50 mg versus placebo in Japanese people with type 1 diabetes mellitus (T1DM) inadequately controlled with insulin. Materials and methods We conducted a multicentre, double-blind, parallel-group, placebo-controlled phase 3 study. Participants (N = 175) were randomized (2:1) to receive once-daily ipragliflozin 50 mg (n = 115) or placebo (n = 60), combined with insulin, for 24 weeks. The primary endpoint was change in glycated haemoglobin (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) -3.8 mmol/mol (95% confidence interval [CI] -6.2, -1.5) or - 0.36% (95% CI -0.57, -0.14; 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 hypoglycaemia 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 participant in this study. Conclusions Daily ipragliflozin 50 mg in combination with insulin significantly reduced HbA1c, daily insulin dose and body weight versus placebo in people with T1DM. No safety concerns were identified after 24 weeks of treatment. Overall, once-daily ipragliflozin 50 mg was both efficacious and well tolerated.