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Diabetes Care. 2018 Sep;41(9):1938-1946. doi: 10.2337/dc18-0623. Epub 2018 Jul 19.

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.

Collaborators (149)

Luquez C, Manghi FP, Ulla MR, Moisello MA, Visco V, De Lapertoza SG, Solis SE, Farias J, Sposetti G, Gillard P, Abrams P, van Ypersele de Strihou M, Conway J, Pedersen S, Senior P, Liutkus JF, Yip CE, Punthakee Z, Bernier F, Lochnan H, Woo V, Elliott T, Palma J, Merino CS, Vargas AD, Wendisch U, Reichel A, Seufert J, Becker B, Alawi H, Birkenfeld AL, Hasslacher C, Luedemann J, Schaum T, Marck C, Sauter J, Aigner U, Onishi Y, Seino H, Sato Y, Nunoi K, Yamauchi A, Nakashima E, Ikeda H, Shiraiwa T, Yamasaki Y, Yokoyama H, Nakamura K, Noritake M, Miyauchi S, Hakoda T, Hirohata Y, Hasegawa A, Fukumoto Y, Nagashima H, Takihata M, Kamada T, Jinnouchi H, Ono Y, Watanabe T, Ohashi H, Takai M, Seguchi T, Yamazaki K, Maeda H, Iwasaki S, De Valk HW, Kooy A, Landewe-Cleuren S, Madziarska K, Stankiewicz A, Wasilewska K, Rudofsky G, Malecki M, Pankowska E, Szyprowska E, Lukaszewicz M, Tokarska L, Bondar I, Karpova I, Ruyatkina L, Zalevskaya A, Sardinov R, Khalimov Y, Sjoberg F, Koskinen P, Curiac D, Lind M, Bach-Kliegel B, Schultes B, Issa BG, Kilvert A, Pereira O, Bain S, Mishra B, Bhatnagar D, Chuck L, Gorson D, Robertson D, Casaubon L, Chaykin L, Frias JP, Hsia S, Jenders R, Lerman S, Segel S, Weissman P, Chang A, Reed J, Madu IJ, Bressler P, Abbott L, Gangi S, Wheeler K, Cohen K, Biggs W, Jabbour S, Karounos D, Menon S, Miers W, Aleppo G, Lefebvre G, Sugimoto D, Ferraro R, Kelly R, Twahirwa M, Case C, Klonoff D, Denker P, Hollander P, Welch M, Leinung M, Kotek L, McGill J, Shlesinger Y, Huffman C, Aronoff S, Lorber D, Terrelonge A, Akhrass F, Bredefeld C, Hershon K, Lenhard J, Donovan D, Stonesifer L, Greenberg C, Ipp E, Bhargava A, Bao S.

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.

PMID:
30026335
DOI:
10.2337/dc18-0623
[Indexed for MEDLINE]

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