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
Author:
Mathieu Chantal1ORCID, Dandona Paresh2ORCID, Gillard Pieter1ORCID, Senior Peter3, Hasslacher Christoph4, Araki Eiichi5, Lind Marcus67ORCID, Bain Stephen C.8, Jabbour Serge9ORCID, Arya Niki10, Hansen Lars11, Thorén Fredrik12, Langkilde Anna Maria12, 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,
Affiliation:
1. Clinical and Experimental Endocrinology, University of Leuven, Leuven, Belgium 2. Department of Medicine, State University of New York at Buffalo, Buffalo, NY 3. Division of Endocrinology, University of Alberta, Edmonton, Canada 4. Diabetesinstitut Heidelberg, Heidelberg, Germany 5. Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan 6. Institute of Medicine, University of Gothenburg, Gothenburg, Sweden 7. Department of Medicine, NU Hospital Group, Uddevalla, Sweden 8. Diabetes Research Unit, Swansea University, Swansea, Wales, U.K. 9. Division of Endocrinology, Diabetes and Metabolic Diseases, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 10. AstraZeneca, Gaithersburg, MD 11. MedImmune, Gaithersburg, MD 12. AstraZeneca, Gothenburg, Sweden
Abstract
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.
Funder
AstraZeneca Bristol-Myers Squibb
Publisher
American Diabetes Association
Subject
Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
206 articles.
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