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
Authors: Mathieu Chantal , Dandona Paresh , Gillard Pieter , Senior Peter , Hasslacher Christoph , Araki Eiichi , Lind Marcus , Bain Stephen C. , Jabbour Serge , Arya Niki , Hansen Lars , Thorén Fredrik , Langkilde Anna Maria ,   DEPICT-2 Investigators, Luquez Cecilia , Manghi Federico Perez , Ulla Maria Rosa , Moisello Maria Alejandra , Visco Virginia , De Lapertoza Silvia Gorban , Solis Silvana Ernestina , Farias Javier , Sposetti Georgina , Gillard Pieter , Abrams Pascale , van Ypersele de Strihou Marina , Conway James , Pedersen Sue , Senior Peter , Liutkus Joanne F. , Yip Churn-Ern , Punthakee Zubin , Bernier Frederic , Lochnan Heather , Woo Vincent , Elliott Thomas , Palma Juan , Merino Carmen Solis , Vargas Alfredo Danin , Wendisch Ulrich , Reichel Andreas , Seufert Jochen , Becker Bernd , Alawi Hasan , Birkenfeld Andreas L. , Hasslacher Christoph , Luedemann Joerg , Schaum Thomas , Marck Cornelia , Sauter Joachim , Aigner Ulrich , Onishi Yukiko , Seino Hiroaki , Sato Yuichi , Nunoi Kiyohide , Yamauchi Akira , Nakashima Eitaro , Ikeda Hiroki , Shiraiwa Toshihiko , Yamasaki Yoshimitsu , Yokoyama Hiroki , Nakamura Kunihiko , Noritake Masayuki , Miyauchi Shozo , Hakoda Tomomi , Hirohata Yoshihide , Hasegawa Atsushi , Fukumoto Yoshihide , Nagashima Hirotaka , Takihata Masahiro , Kamada Tetsuro , Jinnouchi Hideaki , Ono Yuri , Watanabe Takayuki , Ohashi Hiroshi , Takai Masahiko , Seguchi Tadashi , Yamazaki Katsuya , Maeda Hajime , Iwasaki Shingo , De Valk H.W. , Kooy Adriaan , Landewe-Cleuren Sabine , Madziarska Katarzyna , Stankiewicz Andrzej , Wasilewska Katarzyna , Rudofsky Gottfried , Malecki Maciej , Pankowska Ewa , Szyprowska Ewa , Lukaszewicz Monika , Tokarska Lidia , Bondar Irina , Karpova Irina , Ruyatkina Ludmila , Zalevskaya Alsu , Sardinov Ruslan , Khalimov Yury , Sjoberg Folke , Koskinen Pekka , Curiac Dan , Lind Marcus , Bach-Kliegel Birgit , Schultes Bernd , Issa Basil G. , Kilvert Anne , Pereira Olivia , Bain Stephen , Mishra Biswa , Bhatnagar Deepak , Chuck Leonard , Gorson David , Robertson David , Casaubon Luis , Chaykin Louis , Frias Juan Pablo , Hsia Stanley , Jenders Robert , Lerman Sam , Segel Scott , Weissman Peter , Chang Anna , Reed John , Madu Ivy-Joan , Bressler Peter , Abbott Lisa , Gangi Sumana , Wheeler Kate , Cohen Kenneth , Biggs William , Jabbour Serge , Karounos Dennis , Menon Sajeev , Miers Wendell , Aleppo Grazia , Lefebvre Gigi , Sugimoto Danny , Ferraro Robert , Kelly Richard , Twahirwa Marcel , Case Christopher , Klonoff David , Denker Paul , Hollander Priscilla , Welch Michelle , Leinung Matthew , Kotek Larry , McGill Janet , Shlesinger Yshay , Huffman Cynthia , Aronoff Stephen , Lorber Daniel , Terrelonge Antonio , Akhrass Firas , Bredefeld Cindy , Hershon Kenneth , Lenhard James , Donovan Daniel , Stonesifer Larry , Greenberg Craig , Ipp Eli , Bhargava Anuj , Bao Shichun 
Published: July 2018

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 &lt; 0.0001 for all). Mean interstitial glucose, amplitude of glucose excursion, and percent of readings within target glycemic range (&gt;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.