Efficacy and safety of ipragliflozin in Japanese patients with type 2 diabetes stratified by body mass index: A subgroup analysis of five randomized clinical trials

AIMS/INTRODUCTION The influence of overweight/obesity on the clinical efficacy and safety of sodium-glucose co-transporter 2 inhibitors is unclear. We carried out a pooled analysis to examine the impact of body mass index on the efficacy and safety of ipragliflozin. MATERIALS AND METHODS Patient-level data were pooled for five Japanese double-blind trials (NCT00621868, NCT01057628, NCT01135433, NCT01225081 and NCT01242215) in which patients were randomized to ipragliflozin or a placebo as monotherapy, or in combination with metformin, pioglitazone or a sulfonylurea. Outcomes included the changes in hemoglobin A1c, fasting plasma glucose, bodyweight and treatment-emergent adverse events. Patients were divided into four body mass index categories. RESULTS Hemoglobin A1c, fasting plasma glucose and bodyweight decreased significantly in the ipragliflozin group compared with the placebo group in all body mass index categories, and in the total cohort (all P < 0.001). Hemoglobin A1c did not improve in 11.2 and 69.2% of patients in the ipragliflozin and placebo groups, respectively. The change in hemoglobin A1c was weakly correlated with the change in bodyweight in all patients (r = 0.136, P = 0.002). Regarding laboratory variables, the placebo-subtracted difference tended to be greater in patients with higher body mass index for aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase and uric acid. The incidences of treatment-emergent adverse events were similar between the ipragliflozin and placebo groups in all patients combined and in the four body mass index categories. CONCLUSIONS These results show that the efficacy and safety of ipragliflozin are not influenced by obesity/overweight in Japanese patients.