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

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

  • Lancet. 2019 Jul 13;394(10193):121-130. doi: 10.1016/S0140-6736(19)31149-3.
Hertzel C Gerstein 1,  Helen M Colhoun 2,  Gilles R Dagenais 3,  Rafael Diaz 4,  Mark Lakshmanan 5,  Prem Pais 6,  Jeffrey Probstfield 7,  Jeffrey S Riesmeyer 5,  Matthew C Riddle 8,  Lars Rydén 9,  Denis Xavier 6,  Charles Messan Atisso 5,  Leanne Dyal 10,  Stephanie Hall 10,  Purnima Rao-Melacini 10,  Gloria Wong 10,  Alvaro Avezum 11,  Jan Basile 12,  Namsik Chung 13,  Ignacio Conget 14,  William C Cushman 15,  Edward Franek 16,  Nicolae Hancu 17,  Markolf Hanefeld 18,  Shaun Holt 19,  Petr Jansky 20,  Matyas Keltai 21,  Fernando Lanas 22,  Lawrence A Leiter 23,  Patricio Lopez-Jaramillo 24,  Ernesto German Cardona Munoz 25,  Valdis Pirags 26,  Nana Pogosova 27,  Peter J Raubenheimer 28,  Jonathan E Shaw 29,  Wayne H-H Sheu 30,  Theodora Temelkova-Kurktschiev 31,  REWIND Investigators
PMID: 31189511 DOI: 10.1016/S0140-6736(19)31149-3
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.

Figures
Products