Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 52-week results from a randomized controlled trial

AIMS: To investigate the long-term efficacy and safety of dapagliflozin as an adjunct to adjustable insulin in adults with type 1 diabetes (T1D) and inadequate glycemic control. MATERIALS AND METHODS: DEPICT-2 (Dapagliflozin Evaluation in Patients with Inadequately Controlled T1D; NCT02460978) was a placebo-controlled, double-blind, multicenter, Phase III study of adults with T1D (HbA1c 7.5-10.5%) randomized (1:1:1) to receive dapagliflozin 5 mg, 10 mg, or placebo. The efficacy and safety of dapagliflozin over 52 weeks were exploratory endpoints in this extension to DEPICT-2. RESULTS: Of 813 participants randomized, 88.2% completed the study. From baseline to 52 weeks, dapagliflozin 5 and 10 mg were associated with reduction in HbA1c (difference [95% CI] vs. placebo: -0.20% [-0.34, -0.06] and - 0.25% [-0.38, -0.11], respectively) and adjusted mean percentage change in body weight (difference [95% CI] vs. placebo: -4.42% [-5.19, -3.64], and - 4.86% [-5.63, -4.08], respectively). Serious adverse events were reported in the dapagliflozin 5 mg, 10 mg, and placebo groups (32 [11.8%], 19 [7.0%], and 16 [5.9%], respectively). The proportion of hypoglycemic events was similar across groups; severe hypoglycemia was uncommon. More participants with events adjudicated as definite diabetic ketoacidosis (DKA) were in the dapagliflozin 5 and 10 mg groups vs. placebo (11 [4.1%], 10 [3.7%] and 1 [0.4%], respectively); the majority of events were mild or moderate in severity and all resolved with treatment. CONCLUSIONS: Dapagliflozin led to long-term reductions in HbA1c and body weight in adults with T1D, but increased DKA risk compared with placebo.