Efficacy and safety of ipragliflozin as add‐on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a multi‐centre, randomized, placebo‐controlled, double‐blind study

AIMS: To examine the efficacy and safety of add‐on ipragliflozin in Japanese patients with type 2 diabetes in the early stage of insulin therapy. METHODS: Patients treated with insulin (bolus component <30% of total daily dose) with/without a dipeptidyl peptidase‐4 (DPP‐4) inhibitor were randomized to receive placebo (n = 87) or ipragliflozin (n = 175) for 16 weeks. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline. Secondary endpoints included changes in fasting plasma glucose (FPG) and metabolic hormones. Safety endpoints were also examined. RESULTS: The changes in HbA1c were 0.27% and −0.79% (2.9 and −8.7 mmol/mol) in the placebo and ipragliflozin groups, respectively (baseline: 8.62% vs 8.67% [70.8 vs 71.2 mmol/mol]), corresponding to an adjusted mean difference of −1.07% (95% confidence interval −1.24, −0.91) or −11.7 mmol/mol (−13.5, −9.9), p < .001. Ipragliflozin reduced FPG and serum C‐peptide levels and body weight (all p < .001), and increased serum adiponectin levels (p = .022). There was a statistically significant interaction for use/non‐use of a DPP‐4 inhibitor × treatment group for the change in HbA1c (p = .042). Hypoglycaemia was the only treatment‐related adverse event reported in >5% of patients (14.9% vs 29.1%). Events consistent with urinary tract infection (placebo 1.1% vs ipragliflozin 2.3%) or genital infection (0.0% and 4.0%, respectively) occurred in <5% of patients. CONCLUSION: Ipragliflozin was well tolerated and effective in insulin‐treated patients, especially when used with a DPP‐4 inhibitor.