Remogliflozin Etabonate,a Selective Inhibitor of the Sodium-Glucose Transporter 2, Improves Serum Glucose Profiles in Type 1 Diabetes

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.Remogliflozin etabonate (RE) is an oral prodrug of remogliflozin (1), a selective antagonist of the sodium-dependent glucose transporter 2 (SGLT2) located in renal proximal tubules (2–4). It lowers glucose concentrations in type 2 diabetes by inhibiting renal glucose reabsorption (5). Because this mechanism functions independently of insulin, RE could be an effective oral adjunct to insulin for treatment of type 1 diabetes. This clinical trial evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RE administered to subjects with type 1 diabetes. This is the first report of administration of an SGLT2 inhibitor in this patient population.