RT Journal Article
SR Electronic
T1 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
JF Diabetes Care
JO Diabetes Care
FD American Diabetes Association
SP 1938
OP 1946
DO 10.2337/dc18-0623
VO 41
IS 9
A1 Mathieu, Chantal
A1 Dandona, Paresh
A1 Gillard, Pieter
A1 Senior, Peter
A1 Hasslacher, Christoph
A1 Araki, Eiichi
A1 Lind, Marcus
A1 Bain, Stephen C.
A1 Jabbour, Serge
A1 Arya, Niki
A1 Hansen, Lars
A1 Thorén, Fredrik
A1 Langkilde, Anna Maria
YR 2018
UL http://care.diabetesjournals.org/content/41/9/1938.abstract
AB 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 (HbA1c 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 HbA1c (primary outcome; difference vs. placebo: dapagliflozin 5 mg −0.37% [95% CI −0.49, −0.26], dapagliflozin 10 mg –0.42% [−0.53, −0.30]), total daily insulin dose (−10.78% [−13.73, −7.72] and −11.08% [−14.04, −8.02], respectively), and body weight (−3.21% [−3.96, −2.45] and −3.74% [−4.49, −2.99], 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 HbA1c ≥0.5% without severe hypoglycemia compared with placebo. Adverse events were reported for 72.7%, 67.0%, and 63.2% of patients receiving dapagliflozin 5 mg, 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.