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: Chantal Mathieu, Paresh Dandona, Pieter Gillard, Peter Senior, Christoph Hasslacher, Eiichi Araki, Marcus Lind, Stephen C. Bain, Serge Jabbour, Niki Arya, Lars Hansen, Fredrik Thorén, Anna Maria Langkilde, Cecilia Luquez, Federico Perez Manghi, Maria Rosa Ulla, Maria Alejandra Moisello, Virginia Visco, Silvia Gorban De Lapertoza, Silvana Ernestina Solis, Javier Farias, Georgina Sposetti, Pieter Gillard, Pascale Abrams, Marina van Ypersele de Strihou, James Conway, Sue Pedersen, Peter Senior, Joanne F. Liutkus, Churn-Ern Yip, Zubin Punthakee, Frederic Bernier, Heather Lochnan, Vincent Woo, Thomas Elliott, Juan Palma, Carmen Solis Merino, Alfredo Danin Vargas, Ulrich Wendisch, Andreas Reichel, Jochen Seufert, Bernd Becker, Hasan Alawi, Andreas L. Birkenfeld, Christoph Hasslacher, Joerg Luedemann, Thomas Schaum, Cornelia Marck, Joachim Sauter, Ulrich Aigner, Yukiko Onishi, Hiroaki Seino, Yuichi Sato, Kiyohide Nunoi, Akira Yamauchi, Eitaro Nakashima, Hiroki Ikeda, Toshihiko Shiraiwa, Yoshimitsu Yamasaki, Hiroki Yokoyama, Kunihiko Nakamura, Masayuki Noritake, Shozo Miyauchi, Tomomi Hakoda, Yoshihide Hirohata, Atsushi Hasegawa, Yoshihide Fukumoto, Hirotaka Nagashima, Masahiro Takihata, Tetsuro Kamada, Hideaki Jinnouchi, Yuri Ono, Takayuki Watanabe, Hiroshi Ohashi, Masahiko Takai, Tadashi Seguchi, Katsuya Yamazaki, Hajime Maeda, Shingo Iwasaki, H.W. De Valk, Adriaan Kooy, Sabine Landewe-Cleuren, Katarzyna Madziarska, Andrzej Stankiewicz, Katarzyna Wasilewska, Gottfried Rudofsky, Maciej Malecki, Ewa Pankowska, Ewa Szyprowska, Monika Lukaszewicz, Lidia Tokarska, Irina Bondar, Irina Karpova, Ludmila Ruyatkina, Alsu Zalevskaya, Ruslan Sardinov, Yury Khalimov, Folke Sjoberg, Pekka Koskinen, Dan Curiac, Marcus Lind, Birgit Bach-Kliegel, Bernd Schultes, Basil G. Issa, Anne Kilvert, Olivia Pereira, Stephen Bain, Biswa Mishra, Deepak Bhatnagar, Leonard Chuck, David Gorson, David Robertson, Luis Casaubon, Louis Chaykin, Juan Pablo Frias, Stanley Hsia, Robert Jenders, Sam Lerman, Scott Segel, Peter Weissman, Anna Chang, John Reed, Ivy-Joan Madu, Peter Bressler, Lisa Abbott, Sumana Gangi, Kate Wheeler, Kenneth Cohen, William Biggs, Serge Jabbour, Dennis Karounos, Sajeev Menon, Wendell Miers, Grazia Aleppo, Gigi Lefebvre, Danny Sugimoto, Robert Ferraro, Richard Kelly, Marcel Twahirwa, Christopher Case, David Klonoff, Paul Denker, Priscilla Hollander, Michelle Welch, Matthew Leinung, Larry Kotek, Janet McGill, Yshay Shlesinger, Cynthia Huffman, Stephen Aronoff, Daniel Lorber, Antonio Terrelonge, Firas Akhrass, Cindy Bredefeld, Kenneth Hershon, James Lenhard, Daniel Donovan, Larry Stonesifer, Craig Greenberg, Eli Ipp, Anuj Bhargava, Shichun Bao
Journal: Diabetes Care (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 &amp;lt; 0.0001 for all). Mean interstitial glucose, amplitude of glucose excursion, and percent of readings within target glycemic range (&amp;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.