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

abstract

  • 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 A1c (HbA1c) 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 HbA1c 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.

authors

  • Gerstein, HC
  • Colhoun, HM
  • Dagenais, GR
  • Diaz, R
  • Lakshmanan, M
  • Pais, P
  • Probstfield, J
  • Riesmeyer, JS
  • Riddle, MC
  • Rydén, L
  • Xavier, D
  • Atisso, CM
  • Dyal, L
  • Hall, S
  • Rao-Melacini, P
  • Wong, G
  • Avezum, A
  • Basile, J
  • Chung, N
  • Conget, I
  • Cushman, WC
  • Franek, E
  • Hancu, N
  • Hanefeld, M
  • Holt, S
  • Jansky, P
  • Keltai, M
  • Lanas, F
  • Leiter, LA
  • Lopez-Jaramillo, P
  • Cardona Munoz, EG
  • Pirags, V
  • Pogosova, N
  • Raubenheimer, PJ
  • Shaw, Jonathan E
  • Sheu, WHH
  • Temelkova-Kurktschiev, T
  • Abella, M
  • Alebuena, A
  • Almagro, S
  • Amoroso, E
  • Anadon, P
  • Andreu, E
  • Aristimuño, G
  • Arzadun, M
  • Barbieri, M
  • Barcudi, R
  • Bartolacci, I
  • Bolobanich, G
  • Bordonava, A
  • Bustamante Labarta, M
  • Bustos, B
  • Caccavo, A
  • Camino, A
  • Cantero, M
  • Carignano, M
  • Cartasegna, L
  • Cipullo, M
  • Commendatore, V
  • Conosciuto, V
  • Costamagna, O
  • Crespo, C
  • Cuello, J
  • Cuneo, C
  • Cusimano, S
  • Dean, S
  • Dituro, C
  • Dominguez, A
  • Farah, M
  • Fernandez, A
  • Fernandez, F
  • Ferrari, A
  • Flammia, P
  • Fuentealba, J
  • Gallardo, KB
  • Garcia, C
  • Garcia Duran, R
  • Garrido, M
  • Gavicola, R
  • Gerbaudo, C
  • Gilli, G
  • Giotto, AP
  • Godoy Bolzán, P
  • Gomez Vilamajo, O
  • Guerlloy, F
  • Guridi, C
  • Gutierrez Garrido, N
  • Hasbani, E
  • Hermida, S
  • Hominal, M
  • Hrabar, A
  • Ingaramo, A
  • Izzicupo, A
  • Krynski, M
  • Lagrutta, M
  • Lanchiotti, P
  • Langhe, M
  • Leonard, V
  • Llanos, J
  • Lopez Santi, R

publication date

  • 2019

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