Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial

DEPICT-1 Investigators

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93 Citations (Scopus)

Abstract

Background Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. Methods DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18–75 years and had inadequately controlled type 1 diabetes (HbA1c between ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment. After an 8 week lead-in period to optimise diabetes management, patients were randomly assigned (1:1:1) using an interactive voice response system to dapagliflozin 5 mg or 10 mg once daily, given orally, or matched placebo. Randomisation was stratified by current use of continuous glucose monitoring, method of insulin administration, and baseline HbA1c. The primary efficacy outcome was the change from baseline in HbA1c after 24 weeks of treatment in the full analysis set, which consisted of all randomly assigned patients who received at least one dose of study drug. An additional 55 patients who were incorrectly and non-randomly allocated to only dapagliflozin treatment groups were included in the safety analysis set. This study was registered with ClinicalTrials.gov, number NCT02268214; data collection for the present analysis was completed on Jan 4, 2017, and a 28 week extension phase is ongoing. Findings Between Nov 11, 2014, and April 16, 2016, 833 patients were assigned to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260]; 778 of these patients were randomly assigned and included in the full analysis set for efficacy analyses (259 vs 259 vs 260; difference due to randomisation error affecting 55 patients). Mean baseline HbA1c was 8·53% (70 mmol/mol; SD 0·67% [7·3 mmol/mol]). At week 24, both doses of dapagliflozin significantly reduced HbA1c compared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0·42% [95% CI −0·56 to −0·28; p<0·0001] and for dapagliflozin 10 mg vs placebo was −0·45% [−0·58 to −0·31; p<0·0001]). Among patients in the dapagliflozin 5 mg (n=277), dapagliflozin 10 mg (n=296), and placebo (n=260) groups, the most common adverse events were nasopharyngitis (38 [14%] vs 36 [12%] vs 39 [15%]), urinary tract infection (19 [7%] vs 11 [4%] vs 13 [5%]), upper respiratory tract infection (15 [5%] vs 15 [5%] vs 11 [4%]), and headache (12 [4%] vs 17 [6%] vs 11 [4%]). Hypoglycaemia occurred in 220 (79%), 235 (79%), and 207 (80%) patients in the dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo groups, respectively; severe hypoglycaemia occurred in 21 (8%), 19 (6%), and 19 (7%) patients, respectively. Adjudicated definite diabetic ketoacidosis occurred in four (1%) patients in the dapagliflozin 5 mg group, five (2%) in the dapagliflozin 10 mg group, and three (1%) in the placebo group. Interpretation Our results suggest that dapagliflozin is a promising adjunct treatment to insulin to improve glycaemic control in patients with inadequately controlled type 1 diabetes. Funding AstraZeneca and Bristol-Myers Squibb.

Original languageEnglish (US)
Pages (from-to)864-876
Number of pages13
JournalThe Lancet Diabetes and Endocrinology
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2017

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Type 1 Diabetes Mellitus
Randomized Controlled Trials
Safety
Placebos
Insulin
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Random Allocation
Hypoglycemia
Nasopharyngitis
Sodium-Glucose Transport Proteins
Therapeutics
Diabetic Ketoacidosis
Urinary Tract Infections
Respiratory Tract Infections
Type 2 Diabetes Mellitus
Multicenter Studies
Headache

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

@article{142cbc77144d45a3aaf1680ff7d4654b,
title = "Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1): 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial",
abstract = "Background Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. Methods DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18–75 years and had inadequately controlled type 1 diabetes (HbA1c between ≥7·7{\%} and ≤11·0{\%} [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment. After an 8 week lead-in period to optimise diabetes management, patients were randomly assigned (1:1:1) using an interactive voice response system to dapagliflozin 5 mg or 10 mg once daily, given orally, or matched placebo. Randomisation was stratified by current use of continuous glucose monitoring, method of insulin administration, and baseline HbA1c. The primary efficacy outcome was the change from baseline in HbA1c after 24 weeks of treatment in the full analysis set, which consisted of all randomly assigned patients who received at least one dose of study drug. An additional 55 patients who were incorrectly and non-randomly allocated to only dapagliflozin treatment groups were included in the safety analysis set. This study was registered with ClinicalTrials.gov, number NCT02268214; data collection for the present analysis was completed on Jan 4, 2017, and a 28 week extension phase is ongoing. Findings Between Nov 11, 2014, and April 16, 2016, 833 patients were assigned to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260]; 778 of these patients were randomly assigned and included in the full analysis set for efficacy analyses (259 vs 259 vs 260; difference due to randomisation error affecting 55 patients). Mean baseline HbA1c was 8·53{\%} (70 mmol/mol; SD 0·67{\%} [7·3 mmol/mol]). At week 24, both doses of dapagliflozin significantly reduced HbA1c compared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0·42{\%} [95{\%} CI −0·56 to −0·28; p<0·0001] and for dapagliflozin 10 mg vs placebo was −0·45{\%} [−0·58 to −0·31; p<0·0001]). Among patients in the dapagliflozin 5 mg (n=277), dapagliflozin 10 mg (n=296), and placebo (n=260) groups, the most common adverse events were nasopharyngitis (38 [14{\%}] vs 36 [12{\%}] vs 39 [15{\%}]), urinary tract infection (19 [7{\%}] vs 11 [4{\%}] vs 13 [5{\%}]), upper respiratory tract infection (15 [5{\%}] vs 15 [5{\%}] vs 11 [4{\%}]), and headache (12 [4{\%}] vs 17 [6{\%}] vs 11 [4{\%}]). Hypoglycaemia occurred in 220 (79{\%}), 235 (79{\%}), and 207 (80{\%}) patients in the dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo groups, respectively; severe hypoglycaemia occurred in 21 (8{\%}), 19 (6{\%}), and 19 (7{\%}) patients, respectively. Adjudicated definite diabetic ketoacidosis occurred in four (1{\%}) patients in the dapagliflozin 5 mg group, five (2{\%}) in the dapagliflozin 10 mg group, and three (1{\%}) in the placebo group. Interpretation Our results suggest that dapagliflozin is a promising adjunct treatment to insulin to improve glycaemic control in patients with inadequately controlled type 1 diabetes. Funding AstraZeneca and Bristol-Myers Squibb.",
author = "{DEPICT-1 Investigators} and Paresh Dandona and Chantal Mathieu and Moshe Phillip and Lars Hansen and Griffen, {Steven C.} and Diethelm Tsch{\"o}pe and Fredrik Thor{\'e}n and John Xu and Langkilde, {Anna Maria} and Joseph Proietto and Stephen Stranks and Roger Chen and David O'Neal and Alexia Pape and Mark Forbes and Claire Morbey and Anton Luger and Ursula Hanusch and Christoph Schnack and Evelyn Fliesser-Goerzer and Bertram Hoelzl and Christoph Ebenbichler and Rudolf Prager and {Van Gaal}, Luc and Chris Vercammen and Andre Scheen and Chantal Mathieu and Francis Duyck and Frank Nobels and Johannes Ruige and Naresh Aggarwal and Vincent Woo and Bruno St-Pierre and Richard Dumas and Irene Hramiak and Thomas Elliott and {Krarup Hansen}, Troels and Henriksen, {Jan Erik} and Jeppe Gram and Aina Lihn and Jens Bruun and Juha Saltevo and Jyrki Taurio and Jorma Strand and Timo Valle and Sakari Nieminen and Kirsi Pietilainen and Bruno Guerci and Samy Hadjadj and Bresta Miranda-Palma",
year = "2017",
month = "11",
day = "1",
doi = "10.1016/S2213-8587(17)30308-X",
language = "English (US)",
volume = "5",
pages = "864--876",
journal = "The Lancet Diabetes and Endocrinology",
issn = "2213-8587",
publisher = "Elsevier BV",
number = "11",

}

TY - JOUR

T1 - Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (DEPICT-1)

T2 - 24 week results from a multicentre, double-blind, phase 3, randomised controlled trial

AU - DEPICT-1 Investigators

AU - Dandona, Paresh

AU - Mathieu, Chantal

AU - Phillip, Moshe

AU - Hansen, Lars

AU - Griffen, Steven C.

AU - Tschöpe, Diethelm

AU - Thorén, Fredrik

AU - Xu, John

AU - Langkilde, Anna Maria

AU - Proietto, Joseph

AU - Stranks, Stephen

AU - Chen, Roger

AU - O'Neal, David

AU - Pape, Alexia

AU - Forbes, Mark

AU - Morbey, Claire

AU - Luger, Anton

AU - Hanusch, Ursula

AU - Schnack, Christoph

AU - Fliesser-Goerzer, Evelyn

AU - Hoelzl, Bertram

AU - Ebenbichler, Christoph

AU - Prager, Rudolf

AU - Van Gaal, Luc

AU - Vercammen, Chris

AU - Scheen, Andre

AU - Mathieu, Chantal

AU - Duyck, Francis

AU - Nobels, Frank

AU - Ruige, Johannes

AU - Aggarwal, Naresh

AU - Woo, Vincent

AU - St-Pierre, Bruno

AU - Dumas, Richard

AU - Hramiak, Irene

AU - Elliott, Thomas

AU - Krarup Hansen, Troels

AU - Henriksen, Jan Erik

AU - Gram, Jeppe

AU - Lihn, Aina

AU - Bruun, Jens

AU - Saltevo, Juha

AU - Taurio, Jyrki

AU - Strand, Jorma

AU - Valle, Timo

AU - Nieminen, Sakari

AU - Pietilainen, Kirsi

AU - Guerci, Bruno

AU - Hadjadj, Samy

AU - Miranda-Palma, Bresta

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Background Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. Methods DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18–75 years and had inadequately controlled type 1 diabetes (HbA1c between ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment. After an 8 week lead-in period to optimise diabetes management, patients were randomly assigned (1:1:1) using an interactive voice response system to dapagliflozin 5 mg or 10 mg once daily, given orally, or matched placebo. Randomisation was stratified by current use of continuous glucose monitoring, method of insulin administration, and baseline HbA1c. The primary efficacy outcome was the change from baseline in HbA1c after 24 weeks of treatment in the full analysis set, which consisted of all randomly assigned patients who received at least one dose of study drug. An additional 55 patients who were incorrectly and non-randomly allocated to only dapagliflozin treatment groups were included in the safety analysis set. This study was registered with ClinicalTrials.gov, number NCT02268214; data collection for the present analysis was completed on Jan 4, 2017, and a 28 week extension phase is ongoing. Findings Between Nov 11, 2014, and April 16, 2016, 833 patients were assigned to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260]; 778 of these patients were randomly assigned and included in the full analysis set for efficacy analyses (259 vs 259 vs 260; difference due to randomisation error affecting 55 patients). Mean baseline HbA1c was 8·53% (70 mmol/mol; SD 0·67% [7·3 mmol/mol]). At week 24, both doses of dapagliflozin significantly reduced HbA1c compared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0·42% [95% CI −0·56 to −0·28; p<0·0001] and for dapagliflozin 10 mg vs placebo was −0·45% [−0·58 to −0·31; p<0·0001]). Among patients in the dapagliflozin 5 mg (n=277), dapagliflozin 10 mg (n=296), and placebo (n=260) groups, the most common adverse events were nasopharyngitis (38 [14%] vs 36 [12%] vs 39 [15%]), urinary tract infection (19 [7%] vs 11 [4%] vs 13 [5%]), upper respiratory tract infection (15 [5%] vs 15 [5%] vs 11 [4%]), and headache (12 [4%] vs 17 [6%] vs 11 [4%]). Hypoglycaemia occurred in 220 (79%), 235 (79%), and 207 (80%) patients in the dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo groups, respectively; severe hypoglycaemia occurred in 21 (8%), 19 (6%), and 19 (7%) patients, respectively. Adjudicated definite diabetic ketoacidosis occurred in four (1%) patients in the dapagliflozin 5 mg group, five (2%) in the dapagliflozin 10 mg group, and three (1%) in the placebo group. Interpretation Our results suggest that dapagliflozin is a promising adjunct treatment to insulin to improve glycaemic control in patients with inadequately controlled type 1 diabetes. Funding AstraZeneca and Bristol-Myers Squibb.

AB - Background Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. Methods DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18–75 years and had inadequately controlled type 1 diabetes (HbA1c between ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment. After an 8 week lead-in period to optimise diabetes management, patients were randomly assigned (1:1:1) using an interactive voice response system to dapagliflozin 5 mg or 10 mg once daily, given orally, or matched placebo. Randomisation was stratified by current use of continuous glucose monitoring, method of insulin administration, and baseline HbA1c. The primary efficacy outcome was the change from baseline in HbA1c after 24 weeks of treatment in the full analysis set, which consisted of all randomly assigned patients who received at least one dose of study drug. An additional 55 patients who were incorrectly and non-randomly allocated to only dapagliflozin treatment groups were included in the safety analysis set. This study was registered with ClinicalTrials.gov, number NCT02268214; data collection for the present analysis was completed on Jan 4, 2017, and a 28 week extension phase is ongoing. Findings Between Nov 11, 2014, and April 16, 2016, 833 patients were assigned to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260]; 778 of these patients were randomly assigned and included in the full analysis set for efficacy analyses (259 vs 259 vs 260; difference due to randomisation error affecting 55 patients). Mean baseline HbA1c was 8·53% (70 mmol/mol; SD 0·67% [7·3 mmol/mol]). At week 24, both doses of dapagliflozin significantly reduced HbA1c compared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0·42% [95% CI −0·56 to −0·28; p<0·0001] and for dapagliflozin 10 mg vs placebo was −0·45% [−0·58 to −0·31; p<0·0001]). Among patients in the dapagliflozin 5 mg (n=277), dapagliflozin 10 mg (n=296), and placebo (n=260) groups, the most common adverse events were nasopharyngitis (38 [14%] vs 36 [12%] vs 39 [15%]), urinary tract infection (19 [7%] vs 11 [4%] vs 13 [5%]), upper respiratory tract infection (15 [5%] vs 15 [5%] vs 11 [4%]), and headache (12 [4%] vs 17 [6%] vs 11 [4%]). Hypoglycaemia occurred in 220 (79%), 235 (79%), and 207 (80%) patients in the dapagliflozin 5 mg, dapagliflozin 10 mg, and placebo groups, respectively; severe hypoglycaemia occurred in 21 (8%), 19 (6%), and 19 (7%) patients, respectively. Adjudicated definite diabetic ketoacidosis occurred in four (1%) patients in the dapagliflozin 5 mg group, five (2%) in the dapagliflozin 10 mg group, and three (1%) in the placebo group. Interpretation Our results suggest that dapagliflozin is a promising adjunct treatment to insulin to improve glycaemic control in patients with inadequately controlled type 1 diabetes. Funding AstraZeneca and Bristol-Myers Squibb.

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JF - The Lancet Diabetes and Endocrinology

SN - 2213-8587

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