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Randomized Controlled Trial
. 2020 Sep;22(9):1516-1526.
doi: 10.1111/dom.14060. Epub 2020 May 22.

Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 52-week results from a randomized controlled trial

Chantal Mathieu  1 , Gottfried Rudofsky  2 , Moshe Phillip  3 , Eiichi Araki  4 , Marcus Lind  5   6 , Niki Arya  7 , Fredrik Thorén  8 , Markus F Scheerer  9 , Nayyar Iqbal  7 , Paresh Dandona  10
Affiliations
Randomized Controlled Trial

Long-term efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 study): 52-week results from a randomized controlled trial

Chantal Mathieu et al. Diabetes Obes Metab. 2020 Sep.

Abstract

Aim: To investigate the long-term efficacy and safety of dapagliflozin as an adjunct to adjustable insulin in adults with type 1 diabetes (T1D) and inadequate glycaemic control.

Materials and methods: Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT-2) was a placebo-controlled, double-blind, multicentre, phase III study of adults with T1D (HbA1c 7.5%-10.5%) randomized (1:1:1) to receive dapagliflozin 5, 10 mg, or placebo. The efficacy and safety of dapagliflozin over 52 weeks were exploratory endpoints in this extension to DEPICT-2.

Results: Of 813 participants randomized, 88.2% completed the study. From baseline to 52 weeks, dapagliflozin 5 and 10 mg were associated with reduction in HbA1c (difference [95% CI] vs. placebo: -0.20% [-0.34, -0.06] and -0.25% [-0.38, -0.11], respectively) and adjusted mean percentage change in body weight (difference [95% CI] vs. placebo: -4.42% [-5.19, -3.64] and -4.86% [-5.63, -4.08], respectively). Serious adverse events were reported in the dapagliflozin 5, 10 mg, and placebo groups (32 [11.8%], 19 [7.0%] and 16 [5.9%], respectively). The proportion of hypoglycaemic events was similar across groups; severe hypoglycaemia was uncommon. More participants with events adjudicated as definite diabetic ketoacidosis (DKA) were in the dapagliflozin 5 and 10 mg groups versus placebo (11 [4.1%], 10 [3.7%] and 1 [0.4%], respectively); the majority of events were mild or moderate in severity and all were resolved with treatment.

Conclusions: Dapagliflozin led to long-term reductions in HbA1c and body weight in adults with T1D, but increased DKA risk compared with placebo.

Keywords: dapagliflozin, DEPICT-2, SGLT2 inhibitor, type 1 diabetes.

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Conflict of interest statement

C.M. has served as a consultant or advisory board member for ActoBio Therapeutics, AstraZeneca, Boehringher Ingelheim, Eli Lily and Company, Merck Sharp and Dohme Ltd., Novo Nordisk, Roche and Sanofi, and has also received honorarium from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Novartis, Novo Nordisk and Sanofi. G.R. received honorarium for conducting this clinical trial, as well as from AstraZeneca, Eli Lilly, Novo Nordisk, and Merck Sharp and Dohme, and participated in advisory boards for Merck Sharp and Dohme, AstraZeneca, Eli Lilly and Novo Nordisk. E.A. has participated on advisory panels for Alcon, Astellas Pharma, AstraZeneca, Eli Lilly, Kowa Pharmaceutical, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Sanofi and Terumo Corporation, has received honoraria for lectures from Astellas Pharma, MSD, Ono Pharmaceutical, Novo Nordisk Pharma, and Sanofi, and scholarship grants from Astellas Pharma, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, Novo Nordisk Pharma, Ono Pharmaceutical, Sanofi, Shionogi, Sumitomo Dainippon Pharma and Takeda Pharmaceutical. M.L. has received research grants from AstraZeneca, DexCom, Novo Nordisk and Pfizer, and has been a consultant for or received honoraria from AstraZeneca, DexCom, Eli Lilly, Medtronic, MSD, Novo Nordisk and Rubin Medical. P.D. serves on the advisory boards of AstraZeneca, Novo Nordisk, Sanofi, Boehringer Ingelheim, Merck, Intarcia and AbbVie, and has received research grants from all of these companies, apart from Intarcia. M.P. serves on the advisory boards of Sanofi, Medtronic, Novo Nordisk, Eli Lilly and Pfizer, has received research grants from Medtronic, Novo Nordisk, Roche, Eli Lilly, Merck, Sanofi, Pfizer, Bristol‐Myers Squibb, OPKO, Dexcom, Insulet and Lexicon, and honorarium, consultation and speaker bureau from Sanofi, Medtronic, Novo Nordisk, Eli Lilly, Pfizer, RSP Systems, Qulab Medical, AstraZeneca, Lilly and Insulet, and, in addition, is a stockholder for DreaMed Diabetes, NG Solutions and NutriTeen Professionals. N.A., N.I. and F.T. are employees of AstraZeneca. M.F.S. is an employee of Bayer. At the time of the study, M.F.S. was an employee of AstraZeneca. No other conflicts of interest relevant to this article were reported.

Figures

FIGURE 1
FIGURE 1
(A) Change in HbA1c (%) over 52 weeks; (B) change in total daily insulin dose (TDD) (%) over 52 weeks; (C) change in total body weight (%) over 52 weeks; (D) proportion of participants achieving an HbA1c reduction of ≥0.5%; (E) proportion of participants achieving an HbA1c reduction of ≥0.5% without severe hypoglycaemia (%) over 52 weeks. Week 0‐52 data show adjusted mean change from baseline (standard error); week 56 data are only mean change from baseline. Data are for all participants in the full analysis set. The study's primary and secondary endpoints were assessed in the 24‐week treatment period (indicated by a black line at week 24), and exploratory endpoints were assessed at week 52 in the long‐term 28‐week extension. HbA1c (%): mean (standard deviation [SD]) at baseline was 8.44 (0.69), 8.42 (0.69) and 8.41 (0.64) for dapagliflozin 5, 10 mg and placebo, respectively. Body weight (%): mean (SD) at baseline was 78.7 (17.4), 80.1 (18.3) and 78.9 (18.9) kg for dapagliflozin 5, 10 mg and placebo, respectively. TDD, U (SD) at baseline was 58.19 (27.93), 58.68 (28.26) and 56.57 (25.23) for dapagliflozin 5, 10 mg, and placebo, respectively
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