Abstract
BACKGROUND AND OBJECTIVE: To avoid insulin-induced hypoglycemia and weight gain, the minimum dose of insulin should be used. In this study, therefore, we examined insulin dose reduction by ipragliflozin add-on therapy in Japanese patients with type 2 diabetes mellitus treated with long-acting basal insulin. METHODS: In this multicenter, open-label study, patients received one ipragliflozin 50-mg tablet once daily in combination with basal insulin for 24 weeks. The primary efficacy endpoint was the change and percent change in insulin dose from baseline to Week 24. Secondary efficacy endpoints included changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), glycoalbumin, cholesterol, leptin, adiponectin, C-peptide, glucagon, body weight, and blood pressure, and number of patients achieving withdrawal of insulin at the end of treatment (EOT). Treatment-emergent adverse events (TEAEs) were evaluated for safety. RESULTS: In total, 114 patients were screened, 103 were registered, and 97 completed the study. The mean age was 59 years and 72.8% of patients were male. The mean change in insulin dose from baseline at Week 24 was - 6.6 ± 4.4 units/day (p < 0.001); the mean percent change was - 29.87%. HbA1c, FPG, glycoalbumin, glucagon levels, body weight, and blood pressure significantly decreased from baseline to EOT (p < 0.05). Cholesterol, leptin, and adiponectin were unaffected. One patient was able to stop insulin treatment at Week 16. The incidence of TEAEs was 60.2%. Hypoglycemia (10.7%) and pollakiuria (13.6%) were the most common drug-related TEAEs. Conclusions Once-daily 50-mg ipragliflozin enabled a 30% dose reduction of insulin by Week 24 compared with baseline. No major safety concerns were raised. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02847091).