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Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial

Published on Jun 1, 2019in The Lancet59.10
· DOI :10.1016/S0140-6736(19)31149-3
Hertzel C. Gerstein89
Estimated H-index: 89
(Population Health Research Institute),
Helen M. Colhoun47
Estimated H-index: 47
(Edin.: University of Edinburgh)
+ 1453 AuthorsWilliam Zigrang
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Abstract
Summary 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 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.
  • References (31)
  • Citations (5)
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References31
Newest
#1Hertzel C. Gerstein (Population Health Research Institute)H-Index: 89
#2Helen M. Colhoun (Edin.: University of Edinburgh)H-Index: 47
Last.Lars Rydén (KI: Karolinska Institutet)H-Index: 89
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#1F. Barkas (UoI: University of Ioannina)H-Index: 4
#2Moses Elisaf (UoI: University of Ioannina)H-Index: 61
Last.H. Milionis (UoI: University of Ioannina)H-Index: 13
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#1Malak Almutairi (U of A: University of Alberta)H-Index: 3
#2Rami Al Batran (U of A: University of Alberta)H-Index: 8
Last.John R. Ussher (U of A: University of Alberta)H-Index: 26
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#1Andrei C. Sposito (State University of Campinas)H-Index: 26
#2Otávio Berwanger (Albert Einstein Hospital)H-Index: 3
Last.José Francisco Kerr Saraiva (Pontifícia Universidade Católica de Campinas)H-Index: 11
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Cited By5
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#1Shih-Chieh Shao (NCKU: National Cheng Kung University)H-Index: 1
#2Kai-Cheng Chang (Memorial Hospital of South Bend)H-Index: 1
Last.Edward Chia-Cheng Lai (NCKU: National Cheng Kung University)H-Index: 12
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#1Alexander Kokkinos (UoA: National and Kapodistrian University of Athens)H-Index: 14
#2Dimitrios Tsilingiris (UoA: National and Kapodistrian University of Athens)
Last.Christos S. Mantzoros (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 103
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#1Gaurav S. Gulsin (University of Leicester)
#2Matthew P.M. Graham-Brown (University of Leicester)H-Index: 6
Last.Gerry P. McCann (University of Leicester)H-Index: 20
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#1Irene Caruso (University of Bari)H-Index: 1
#2Angelo Cignarelli (University of Bari)H-Index: 14
Last.Francesco Giorgino (University of Bari)H-Index: 44
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