PMID-31189511 – Dulaglutide REWIND Cardiovascular Outcomes Trial
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130.
Quick Reference
| Property | Value |
|---|---|
| PMID | 31189511 |
| DOI | 10.1016/S0140-6736(19)31149-3 |
| Year | 2019 |
| Journal | The Lancet |
| Study Type | RCT (cardiovascular outcomes trial) |
| Evidence Level | I |
| Sample | n=9,901 patients with T2D (mean age 66 years; 46% women; 31% with prior CVD) |
| Peptide(s) Studied | Dulaglutide |
Key Findings
- Primary 3-point MACE outcome occurred in 12.0% of dulaglutide group vs. 13.4% of placebo group (HR 0.88; 95% CI 0.79-0.99; P=0.026)
- Dulaglutide significantly reduced the composite of non-fatal MI, non-fatal stroke, or CV death
- Stroke was significantly reduced (HR 0.76; 95% CI 0.61-0.95) — the first GLP-1 RA CVOT to show a significant stroke reduction
- All-cause mortality was not significantly different (HR 0.90; 95% CI 0.80-1.01)
- Benefits were consistent regardless of prior CV disease status (69% primary prevention)
- Median follow-up of 5.4 years — the longest of any GLP-1 RA CVOT
Study Design
Multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Patients aged >=50 years with T2D and either prior CVD or CV risk factors were randomized 1:1 to subcutaneous dulaglutide 1.5 mg once weekly or placebo. Event-driven design. Notably, 69% of participants were enrolled based on CV risk factors only (primary prevention), making this the highest primary prevention proportion of any GLP-1 RA CVOT.
Limitations
- Only tested single dose (1.5 mg); higher doses (3.0, 4.5 mg) now available
- Predominantly older population (mean 66 years) limits generalizability to younger patients
- HbA1c at baseline was relatively well-controlled (mean 7.3%), potentially attenuating glycemic benefit
- Median diabetes duration was approximately 10 years
Clinical Relevance
REWIND was the first GLP-1 RA CVOT to demonstrate CV benefit in a predominantly primary prevention population and the first to show significant stroke reduction. The 5.4-year follow-up provides the longest safety and efficacy data from any GLP-1 RA CVOT. These findings support dulaglutide use for CV risk reduction in a broad T2D population, not just those with established CVD.
Related
#research #RCT #evidence-level-I #metabolic #dulaglutide