Trulicity ® (dulaglutid) injektion

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Ger behandling med TRULICITY® (dulaglutid) kardiovaskulära fördelar?

REWIND-studien visade att dulaglutid 1,5 mg minskade MACE-3 signifikant jämfört med placebo.

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Detailed Information

The REWIND study was an event-driven, randomized, double-blind, phase 3 CV outcomes study of dulaglutide.1

The study evaluated the effect on MACE-3 and other serious outcomes with once-weekly dulaglutide 1.5 mg treatment compared with placebo when added to standard of care in participants 50 years of age and older with T2DM and established CV disease and/or risk factors.1

The REWIND trial was sponsored by Eli Lilly and Company, site management and data collection were conducted by ICON Clinical Research, scientific leadership was provided by an international steering committee coordinated by the Population Health Research Institute in Hamilton, Canada, and data analysis was conducted by the Population Health Research Institute.1

Key Inclusion/Exclusion Criteria

Eligible patients had

Age-Specific Inclusion Criteria for REWIND Trial1

Participants age... 

Had to have... 

50-54 y

established CVD. 

55-59 y

established CVD or evidence of other subclinical CVD. 

60 y or older

established CVD, evidence of other subclinical CVD, or at least 2 other CV risk factors.

Abbreviations: CV = cardiovascular; CVD = cardiovascular disease; REWIND = Researching cardiovascular Events with a Weekly INcretin in Diabetes; y = years.

Patients were excluded if they had

  • liver disease
  • a history of pancreatitis
  • gastric emptying abnormalities
  • an eGFR of less than 15 mL/min/1.73m2 or on dialysis
  • a coronary or cerebrovascular event in the last 2 months or plans to revascularize, or
  • history of medullary C-cell hyperplasia or medullary thyroid cancer.1,2

Outcome Measures

The primary outcome was the first occurrence of the composite MACE-3 endpoint which included

  • death due to CV causes,
  • nonfatal MI, or
  • nonfatal stroke.1,2

An external adjudication committee that was blinded to treatment allocation was to adjudicate all deaths, CV, pancreatic, and thyroid events.1,2

Study follow-up continued until 1200 adjudicated events of primary outcomes were confirmed.1,2

Baseline Characteristics

A total of 9901 patients in 24 countries were randomized.1,3

Results

Dulaglutide 1.5 mg significantly reduced MACE-3 when compared to placebo (HR=0.88 [95% CI 0.79, 0.99]; p = .026), demonstrating a decrease in CV events and showing safety in a population that included a majority of participants without established CV disease.2

Each component of MACE-3 is described in Effects of Dulaglutide 1.5 mg on Each Component of the Primary Outcome of MACE-3.

Effects of Dulaglutide 1.5 mg on Each Component of the Primary Outcome of MACE-32

CV Parameter

HR (95% CI)

Nonfatal MI

0.96 (0.79, 1.16)

Nonfatal stroke

0.76 (0.61, 0.95)

CV death

0.91 (0.78, 1.06)

Abbreviations: CV = cardiovascular; HR = hazard ratio; MACE-3 = major adverse cardiovascular events (death due to cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke); MI = myocardial infarction.

The median follow-up time in REWIND was 5.4 years. The safety profile of dulaglutide in REWIND was generally consistent with the GLP-1 receptor agonist class. Dulaglutide did not significantly increase any of the prespecified adverse events of special interest including first study drug discontinuation, serious gastrointestinal events, severe hypoglycemia, cancers, immune reactions, or pancreatitis.2

Differences between the REWIND trial and previous CVOTs

The REWIND trial differs from previous CVOTs with GLP-1 receptor agonists4,5 in several ways

  • REWIND was the only trial that prospectively tested the hypothesis of superiority to placebo with respect to CV events without testing non-inferiority. 2
  • Most of the participants did not have previous CV disease or a previous CV event. 2
  • The 5.4 year median follow-up was much longer than that in the other CVOTs, in which median follow-up ranged from 1.5 years to 3.8 years 4,6
  • Dulaglutide reduces CV events in people with Hb1Ac concentrations both within and higher than guideline-recommended targets, without increasing weight or the risk of hypoglycaemia, and has effect sizes that are similar to those in the other trials with higher baseline HbA1C concentrations. 2

References

1Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Trial Investigators. 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;20(1):42-49. https://doi.org/10.1111/dom.13028

2Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130. https://doi.org/10.1016/S0140-6736(19)31149-3

3Researching cardiovascular events with a weekly incretin in diabetes (REWIND). ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT01394952. Updated January 16, 2018. Accessed July 2, 2018.

4Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet 2018; 392: 1519–29.

5Bethel MA, Patel RA, Merrill P, et al. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. Lancet Diabetes Endocrinol 2018;6: 105–13.

6Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375: 311–22.

Glossary

CV = cardiovascular

eGFR = estimated glomerular filtration rate

HbA1c = glycated hemoglobin

HR = hazard ratio

GLP-1 = glucagon-like peptide-1

MACE = major adverse cardiovascular event

MACE-3 = major adverse cardiovascular events (death due to cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke)

MI = myocardial infarction

REWIND = Researching cardiovascular Events with a Weekly INcretin in Diabetes

T2DM = type 2 diabetes mellitus

Datum fӧr senaste ӧversyn 2020 M07 13


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