Abstract

Objective – To determine if dapagliflozin, which selectively inhibits renal glucose reabsorption, lowers hyperglycemia in type 2 diabetes patients poorly controlled with high insulin doses plus oral antidiabetic agents (OADs).

Research Design and Methods – Randomized, double-blind, three-arm parallel group, placebo-controlled, 26-center trial (United States and Canada). Based on data from an insulin dose-adjustment setting cohort (n = 4), patients in the treatment cohort (n = 71) were randomized 1:1:1 to placebo, 10 and 20 mg dapagliflozin, plus OAD(s) and 50% of their daily insulin dose. Primary outcome was change from baseline in glycated hemoglobin (A1C) at week 12 (dapagliflozin versus placebo, LOCF).

Results – At week 12 (LOCF), dapagliflozin 10- and 20-mg groups demonstrated −0.70% and −0.78% mean differences in A1C change from baseline versus placebo. In both dapagliflozin groups, 65.2% of patients achieved a decrease from baseline in A1C ≥0.5% versus 15.8% in the placebo group. Mean changes from baseline in fasting plasma glucose (FPG) were +17.8, +2.4, and −9.6 mg/dl (placebo, 10 and 20 mg dapagliflozin). Postprandial glucose (PPG) reductions with dapagliflozin also showed dose-dependency. Mean changes in total body weight were −1.9, −4.5, and −4.3 kg (placebo, 10 and 20 mg dapagliflozin). Overall, adverse events were balanced across all groups, although more genital infections occurred in the dapagliflozin 20-mg group than placebo.

Conclusions – In patients on high insulin doses plus insulin sensitizers who had their baseline insulin reduced by 50%, dapagliflozin decreased A1C, produced better FPG and PPG levels, and lowered weight more than placebo.