Abstract
INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors promote urinary glucose excretion. However, the differences in the effects of various SGLT2 inhibitors are unknown. We used flash glucose monitoring (FGM) to identify the differences between tofogliflozin and ipragliflozin in terms of efficacy in reducing glycemic variability and mitigate hypoglycemia risk. METHODS: In this crossover study, 24 patients with type-2 diabetes mellitus (T2DM) receiving insulin glargine U300 therapy were randomly allocated to tofogliflozin and ipragliflozin or ipragliflozin and tofogliflozin group. Glycemic variability and hypoglycemia were compared using to the 3-day FGM data per treatment period. RESULTS: Glucose level 2 h after each meal was significantly lower with tofogliflozin administration than with ipragliflozin administration. Time below the target glucose range after tofogliflozin administration was significantly lower than that after ipragliflozin administration (2.1% ± 4.4% vs. 8.7% ± 11.7%). The 24-h standard deviation of glucose level, mean amplitude of glycemic excursion, and mean percent time with nocturnal hypoglycemia after tofogliflozin administration were significantly lower than those after ipragliflozin administration. CONCLUSIONS: Tofogliflozin was more effective and safer than ipragliflozin in reducing glycemic variability and mitigating hypoglycemia risk in patients with T2DM treated with insulin glargine U300. TRIAL REGISTRATION: This trial was registered at the University Hospital Medical Information Network Clinical Trial Registry (no. UMIN000037158).