Remogliflozin etabonate, a selective inhibitor of the sodium-glucose transporter 2, improves serum glucose profiles in type 1 diabetes

Abstract

Objective: Remogliflozin etabonate (RE), an inhibitor of the sodium-glucose transporter 2, improves glucose profiles in type 2 diabetes. This study assessed safety, tolerability, pharmacokinetics, and pharmacodynamics of RE in subjects with type 1 diabetes.

Research design and methods: Ten subjects managed with continuous subcutaneous insulin infusion were enrolled. In addition to basal insulin, subjects received five randomized treatments: placebo, prandial insulin, 50 mg RE, 150 mg RE, and mg RE 500.

Results: Adverse events and incidence of hypoglycemia with RE did not differ from placebo and prandial insulin groups. RE significantly increased urine glucose excretion and reduced the rise in plasma glucose concentration after oral glucose. RE reduced incremental adjusted weighted mean glucose (0-4 h) values by 42-49 mg/dL and mean glucose (0-10 h) by 52-69 mg/dL.

Conclusions: RE can be safely administered with insulin in type 1 diabetes and reduces plasma glucose concentrations compared with placebo.

Trial registration: ClinicalTrials.gov NCT00575159.

Figures

Figure 1

Mean (± SEM) 12-h serum insulin (A), 12-h plasma glucose (B), and urine glucose (C) profiles observed for each treatment period. After the overnight fast, basal insulin infusion was continued, and each subject received the following five treatments in random order: 1) placebo insulin injection + RE placebo (□; placebo), 2) mealtime insulin injection + RE placebo (○; prandial insulin), 3) placebo insulin injection + RE 50 mg (●; RE 50 mg), 4) placebo insulin injection + RE 150 mg (▲; RE 150 mg), and 5) placebo insulin injection + RE 500 mg (■; RE 500 mg). Relative to RE dosing, the morning glucose challenge, lunch, and supper were scheduled at 0.25, 4.25, and 10.25 h, respectively. All subjects received randomized insulin or placebo injections 15 min before the glucose challenge and lunch plus their regularly prescribed bolus of rapid-acting insulin 15 min before supper.