A Study of Dapagliflozin in Patients With Type 2 Diabetes Receiving High Doses of

Abstract

OBJECTIVE— To determine whether dapagliflozin, which selectively inhibits renal glucose reabsorption, lowers hyperglycemia in patients with type 2 diabetes that is poorly controlled with high insulin doses plus oral antidiabetic agents (OADs). RESEARCHDESIGNANDMETHODS— This was a randomized, double-blind, three- arm parallel-group, placebo-controlled, 26-center trial (U.S. and Canada). Based on data from an insulin dose-adjustment setting cohort (n ? 4), patients in the treatment cohort (n ? 71) were randomly assigned 1:1:1 to placebo, 10 mg dapagliflozin, or 20 mg dapagliflozin, plus OAD(s) and 50% of their daily insulin dose. The primary outcome was change from baseline in A1C at week 12 (dapagliflozin vs. placebo, last observation carried forward [LOCF]). RESULTS— At week 12 (LOCF), the 10- and 20-mg dapagliflozin 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 mg dapagliflozin, and 20 mg dapagliflozin, respec- tively). Postprandial glucose (PPG) reductions with dapagliflozin also showed dose dependence. Mean changes in total body weight were?1.9,?4.5, and?4.3 kg (placebo, 10 mg dapagliflo- zin, and 20 mg dapagliflozin). Overall, adverse events were balanced across all groups, although more genital infections occurred in the 20-mg dapagliflozin group than in the placebo group. CONCLUSIONS— In patients receiving 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. Diabetes