Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves model-based indices of beta cell function in patients with type 2 diabetes

摘要

Aims/hypothesis In rodent models of diabetes, treatment with sodium glucose co-transporter 2 (SGLT2) inhibitors improves beta cell function. This analysis assessed the effects of the SGLT2 inhibitor, canagliflozin, on model-based measures of beta cell function in patients with type 2 diabetes. Methods Data from three Phase 3 studies were analysed, in which: (Study 1) canagliflozin 100 and 300?mg were compared with placebo as monotherapy for 26?weeks; (Study 2) canagliflozin 100 and 300?mg were compared with placebo as add-on to metformin?+?sulfonylurea for 26?weeks; or (Study 3) canagliflozin 300?mg was compared with sitagliptin 100?mg as add-on to metformin?+?sulfonylurea for 52?weeks. In each study, a subset of patients was given mixed-meal tolerance tests at baseline and study endpoint, and model-based beta cell function parameters were calculated from plasma glucose and C-peptide. Results In Studies 1 and 2, both canagliflozin doses increased beta cell glucose sensitivity compared with placebo. Placebo-subtracted least squares mean (LSM) (SEM) changes were 23 (9) and 18 (9) pmol?min?1?m?2 (mmol/l)?1 with canagliflozin 100 and 300?mg, respectively (p??1?m?2 (mmol/l)?1 (p??1?m?2, respectively; p?Trial registration: Clinicaltrials.gov NCT01081834 (Study 1); NCT01106625 (Study 2); NCT01137812 (Study 3)