GLP-1 Evidence

Not medical advice. A record of published research and our assessments of it. The limits

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

Design
Randomized trial · 9901 participants · Hard outcome
Match to healthy normal-weight adults aged 55–75
Different populationAll had type 2 diabetes; notable for including a majority without prior cardiovascular disease and for the longest follow-up of any CVOT (5.4 years). Mean age 66 matches the target age band.
Could weight loss explain it?
PossiblySmall weight (-1.5 kg) and HbA1c effects; benefit similar with and without prior CVD (full text).
Study tier
Study tier 1[Auto] Large randomized trial with clinical outcomes (auto-provisional; risk of bias and consistency not yet assessed).
Assessment
Version 2 · curated · Sep 13, 2026

Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.

In 9,901 people with type 2 diabetes, most without prior heart disease, dulaglutide reduced major cardiovascular events by 12% over 5.4 years; total mortality was not significantly changed. Longest follow-up in the class; still confined to diabetes.

01Findings

What the study reported

Drugs
Dulaglutide
Dose
1.5 mg once weekly
Route
subcutaneous
Treatment duration
median 5.4 years
Comparator
placebo
Primary outcome
Nonfatal MI, nonfatal stroke or CV death
Effect
HR 0.88 (12.0% vs 13.4%); all-cause mortality HR 0.90 (NS)
95% confidence interval
0.79 to 0.99
P value
0.026
Follow-up
median 5.4 years
Adverse events
GI adverse events 47.4% vs 34.1%.
Limitations
Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.

Who was studied

Mean age
66.2
Age min
50
Sex distribution
46.3% female
Diabetes status
type 2 diabetes required
Cvd status
31% prior CVD; remainder risk factors only (full text)
Sample size
4949

Study quality details

Study design
Randomized controlled trial
Sample size
4949
Randomization
yes
Blinding
double-blind
Comparator
placebo
Follow up duration
50 years
Outcome type
mixed
Replication
not assessed (auto)
Consistency with other evidence
not assessed (auto)
Population applicability
INDIRECT
Statistical precision
CI reported: 95% CI 0·79-0·99
Risk of bias
not assessed (auto)
Funding conflicts
yes
Peer review status
yes
02Funding

Funding and conflicts

Funding
Eli Lilly
Industry funded
Yes
Manufacturer
Eli Lilly
Sponsor role
Sponsor designed and analysed.
Author conflicts
Authors report Eli Lilly relationships; sponsor co-authors.
Independent replication
class-level
Notes
Authors declare relationships with the drug's manufacturer: Eli Lilly

Funding is shown on every study and never used to score it.

03Claims

Claims this study bears on

04Source

The source, as retrieved

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.

Where this record came from

SourceRetrievedIdentifier
pubmedSep 13, 202631189511
first ingestion