Active- and placebo-controlled dose-finding study to assess the efficacy, safety, and tolerability of multiple doses of ipragliflozin in patients with type 2 diabetes mellitus.

ABSTRACT

AIM: To evaluate the efficacy, safety, and tolerability of multiple doses of ipragliflozin. This novel selective inhibitor of sodium glucose co-transporter 2 is in clinical development for the treatment of patients with type 2 diabetes mellitus (T2DM). METHODS: In a 12-week, multicenter, double-blind, randomized, active- and placebo-controlled dose-finding study, patients were randomized to one of four ipragliflozin treatment groups (12.5, 50, 150, and 300 mg once daily), placebo, or active control (metformin). The primary efficacy outcome was the mean change from baseline to Week 12 of glycosylated hemoglobin (HbA1c) compared with placebo. RESULTS: Ipragliflozin showed a dose-dependent decrease in HbA1c of -0.49% to -0.81% at Week 12 compared with placebo (P<0.001); a decrease of -0.72% was seen with metformin. Among the ipragliflozin groups there was also a dose-dependent reduction in body weight of up to 1.7 kg. Proportions of patients experiencing treatment-emergent adverse events were similar across all groups ipragliflozin (45.7-58.8%), placebo (62.3%), and metformin (59.4%). No clinically relevant effects were observed for other safety measures. CONCLUSIONS: After 12 weeks of treatment, ipragliflozin dose-dependently decreased HbA1c, with ipragliflozin ≥50 mg/day in patients with T2DM; an effect comparable to metformin. No safety or tolerability concerns were identified.