Effects of luseogliflozin, a sodium–glucose co‐transporter 2 inhibitor, on 24‐h glucose variability assessed by continuous glucose monitoring in Japanese patients with type 2 diabetes mellitus: a randomized, double‐blind, placebo‐controlled, crossover study

Abstract

The aim of the present study was to determine the effects of luseogliflozin on 24‐h glucose levels, assessed by continuous glucose monitoring, and on pharmacodynamic variables measured throughout the day. In this double‐blind, placebo‐controlled, crossover study, 37 patients with type 2 diabetes mellitus inadequately controlled with diet and exercise were randomized into two groups. Patients in each group first received luseogliflozin then placebo for 7 days each, or vice versa. After 7 days of treatment, the mean 24‐h glucose level was significantly lower with luseogliflozin than with placebo [mean (95% confidence interval) 145.9 (134.4–157.5) mg/dl vs 168.5 (156.9–180.0) mg/dl; p < 0.001]. The proportion of time spent with glucose levels ≥70 to ≤180 mg/dl was significantly greater with luseogliflozin than with placebo [median (interquartile range) 83.2 (67.7–96.5)% vs 71.9 (46.9–83.3)%; p < 0.001] without inducing hypoglycaemia. The decrease in glucose levels was accompanied by reductions in serum insulin levels throughout the day.

Sodium‐glucose cotransporter 2 inhibitor luseogliflozin improves glycaemic control, assessed by continuous glucose monitoring, even on a low‐carbohydrate diet

“…Consistent with our earlier report , the administration of luseogliflozin with the NCD reduced glucose concentrations throughout the day. Although the glucose concentrations were lower with the LCD than with the NCD during the placebo period, luseogliflozin further reduced the glucose concentrations throughout the day with the LCD relative to placebo.…”

“…In the present randomized, double‐blind, placebo‐controlled, crossover study, Japanese patients with T2D who agreed to participate in an optional extension to our previous study were randomized into two groups. The patients received luseogliflozin followed by placebo for 8 days each (L/P group), or vice versa (P/L group).…”

CV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” Hypothesis

“…Concomitantly, both fasting and postmeal plasma b-hydroxybutyrate concentrations were increased twofold to threefold; these changes were similar in time course, though attenuated in extent, in a group of nondiabetic volunteers receiving the drug. Similar results have been reported in Japanese patients with T2D with the use of empagliflozin, tofogliflozin, luseogliflozin, or canagliflozin (28)(29)(30)(31)(32). For example, in a 24-week phase III study of drug-naive patients with T2D (32), plasma ketones rose dose dependently with the administration of 100 or 200 mg canagliflozin versus placebo throughout the study period.…”

“…For example, in a 24-week phase III study of drug-naive patients with T2D (32), plasma ketones rose dose dependently with the administration of 100 or 200 mg canagliflozin versus placebo throughout the study period. Of note, though mean plasma ketone levels are only modestly elevated, in a sizeable proportion of subjects they rise into the millimolar range (27)(28)(29)(30)(31)(32), particularly in the more insulinopenic patients (27).…”

Sodium‐glucose co‐transporter‐2 inhibitor use and dietary carbohydrate intake in Japanese individuals with type 2 diabetes: A randomized, open‐label, 3‐arm parallel comparative, exploratory study

“…Luseogliflozin improved AUC 0‐48h and mean of CGM data in all 3 groups, indicating that differences in carbohydrate content (55% vs 40% of TEC) and GI (white rice vs brown rice) did not affect the glucose‐lowering effects. Luseogliflozin did not affect SD or MAGE values, confirming that SGLT2 inhibitors improve glycaemia without affecting glucose variability …”