Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide

Diabetes Obes Metab. 2018 Jan;20(1):42-49. doi: 10.1111/dom.13028. Epub 2017 Jul 14.

Abstract

The aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. Follow-up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle-aged patient seen in general practice throughout the world.

Trial registration: ClinicalTrials.gov NCT01394952.

Keywords: GLP-1 receptor agonist; antidiabetic drug; cardiovascular disease; clinical trial; diabetes complications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / adverse effects
  • Delayed-Action Preparations / therapeutic use
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Angiopathies / epidemiology
  • Diabetic Angiopathies / mortality
  • Diabetic Angiopathies / prevention & control*
  • Diabetic Cardiomyopathies / epidemiology
  • Diabetic Cardiomyopathies / mortality
  • Diabetic Cardiomyopathies / prevention & control*
  • Drug Administration Schedule
  • Drug Therapy, Combination / adverse effects
  • Female
  • Follow-Up Studies
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucagon-Like Peptides / administration & dosage
  • Glucagon-Like Peptides / adverse effects
  • Glucagon-Like Peptides / analogs & derivatives*
  • Glucagon-Like Peptides / therapeutic use
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Immunoglobulin Fc Fragments / administration & dosage
  • Immunoglobulin Fc Fragments / adverse effects
  • Immunoglobulin Fc Fragments / therapeutic use*
  • Incretins / administration & dosage
  • Incretins / adverse effects
  • Incretins / therapeutic use*
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Mortality
  • Multicenter Studies as Topic
  • Randomized Controlled Trials as Topic
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Research Design
  • Risk Factors

Substances

  • Delayed-Action Preparations
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Incretins
  • Recombinant Fusion Proteins
  • hemoglobin A1c protein, human
  • Glucagon-Like Peptides
  • dulaglutide

Associated data

  • ClinicalTrials.gov/NCT01394952