TY - JOUR
T1 - Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND)
T2 - a double-blind, randomised placebo-controlled trial
AU - REWIND Investigators
AU - Gerstein, Hertzel C.
AU - Colhoun, Helen M.
AU - Dagenais, Gilles R.
AU - Diaz, Rafael
AU - Lakshmanan, Mark
AU - Pais, Prem
AU - Probstfield, Jeffrey
AU - Riesmeyer, Jeffrey S.
AU - Riddle, Matthew C.
AU - Rydén, Lars
AU - Xavier, Denis
AU - Atisso, Charles Messan
AU - Dyal, Leanne
AU - Hall, Stephanie
AU - Rao-Melacini, Purnima
AU - Wong, Gloria
AU - Avezum, Alvaro
AU - Basile, Jan
AU - Chung, Namsik
AU - Conget, Ignacio
AU - Cushman, William C.
AU - Franek, Edward
AU - Hancu, Nicolae
AU - Hanefeld, Markolf
AU - Holt, Shaun
AU - Jansky, Petr
AU - Keltai, Matyas
AU - Lanas, Fernando
AU - Leiter, Lawrence A.
AU - Lopez-Jaramillo, Patricio
AU - Cardona Munoz, Ernesto German
AU - Pirags, Valdis
AU - Pogosova, Nana
AU - Raubenheimer, Peter J.
AU - Shaw, Jonathan E.
AU - Sheu, Wayne H.H.
AU - Temelkova-Kurktschiev, Theodora
AU - Abella, Mercedes
AU - Alebuena, Andrea
AU - Almagro, Sandra
AU - Amoroso, Eduardo
AU - Anadon, Paula
AU - Andreu, Elizabeth
AU - Aristimuño, Guillermo
AU - Arzadun, Maria
AU - Barbieri, Maria
AU - Barcudi, Raul
AU - Bartolacci, Ines
AU - Chow, Lisa
AU - Seaquist, Elizabeth
N1 - Funding Information:
The trial was sponsored and funded by Eli Lilly and Company led by an international steering committee coordinated by the Population Health Research Institute in Hamilton, Canada, which also did all data analyses. Site management and data collection were provided by ICON Clinical Research. Scientists employed by the funder were on the steering committee and contributed to trial design, trial implementation, and data interpretation. All authors and the sponsor jointly made the decision to submit for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/7/13
Y1 - 2019/7/13
N2 - BACKGROUND: Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A
1c (HbA
1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control.
METHODS: This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952.FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA
1c 7·2% [IQR 6·6-8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1-5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79-0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80-1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p<0·0001).
INTERPRETATION: Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors.FUNDING: Eli Lilly and Company.
AB - BACKGROUND: Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A
1c (HbA
1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control.
METHODS: This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952.FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA
1c 7·2% [IQR 6·6-8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1-5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79-0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80-1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p<0·0001).
INTERPRETATION: Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors.FUNDING: Eli Lilly and Company.
KW - Aged
KW - Cardiovascular Diseases/mortality
KW - Diabetes Mellitus, Type 2/complications
KW - Double-Blind Method
KW - Female
KW - Glucagon-Like Peptides/analogs & derivatives
KW - Humans
KW - Hypoglycemic Agents/therapeutic use
KW - Immunoglobulin Fc Fragments/therapeutic use
KW - Male
KW - Middle Aged
KW - Myocardial Infarction/prevention & control
KW - Recombinant Fusion Proteins/therapeutic use
KW - Stroke/prevention & control
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U2 - 10.1016/S0140-6736(19)31149-3
DO - 10.1016/S0140-6736(19)31149-3
M3 - Article
C2 - 31189511
AN - SCOPUS:85068151338
SN - 0140-6736
VL - 394
SP - 121
EP - 130
JO - The Lancet
JF - The Lancet
IS - 10193
ER -
