Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 24-week results from a randomized controlled trial

OBJECTIVE: This 24-week, double-blinded, phase 3 clinical trial (DEPICT-2; ClinicalTrials.gov, NCT02460978) evaluated efficacy and safety of dapagliflozin as adjunct therapy to adjustable insulin in patients with inadequately controlled type 1 diabetes (HbA_1c 7.5-10.5%). RESEARCH DESIGN AND METHODS: Patients were randomized 1:1:1 to dapagliflozin 5 mg (n = 271), dapagliflozin 10 mg (n = 270), or placebo (n = 272) plus insulin. Insulin dose was adjusted by investigators according to self-monitored glucose readings, local guidance, and individual circumstances. RESULTS: Baseline characteristics were balanced between treatment groups. At week 24, dapagliflozin significantly decreased HbA_1c (primary outcome; difference vs. placebo: dapagliflozin 5 mg 20.37% [95% CI 20.49, 20.26], dapagliflozin 10 mg-0.42% [20.53, 20.30]), total daily insulin dose (210.78% [213.73, 27.72] and 211.08% [214.04, 28.02], respectively), and body weight (23.21% [23.96, 22.45] and 23.74% [24.49, 22.99], respectively) (P < 0.0001 for all). Mean interstitial glucose, amplitude of glucose excursion, and percent of readings within target glycemic range (>70 to ≤180 mg/dL) versus placebo were significantly improved. More patients receiving dapagliflozin achieved a reduction in HbA_1c ≥0.5% without severe hypoglycemia compared with placebo. Adverse events were reported for 72.7%, 67.0%, and 63.2%ofpatients receiving dapagliflozin 5mg, dapagliflozin 10 mg, and placebo, respectively. Hypoglycemia, including severe hypoglycemia, was balanced between groups. There were more adjudicated definite diabetic ketoacidosis (DKA) events with dapagliflozin: 2.6%, 2.2%, and 0% for dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo, respectively. CONCLUSIONS: Dapagliflozin as adjunct therapy to adjustable insulin in patients with type 1 diabetes was well tolerated and improved glycemic control with no increase in hypoglycemia versus placebo but with more DKA events.