PMID-27633186 – SUSTAIN 6 Semaglutide Cardiovascular Outcomes in T2D
Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine, 2016;375(19):1834-1844.
Quick Reference
| Property | Value |
|---|---|
| PMID | 27633186 |
| DOI | 10.1056/NEJMoa1607141 |
| Year | 2016 |
| Journal | New England Journal of Medicine |
| Study Type | RCT |
| Evidence Level | I |
| Sample | n=3,297 patients with type 2 diabetes and high cardiovascular risk |
| Peptide(s) Studied | Semaglutide |
Key Findings
- Semaglutide reduced the primary composite MACE endpoint by 26% vs placebo (HR 0.74; 95% CI 0.58-0.95; p<0.001 for noninferiority; p=0.02 for superiority)
- Nonfatal stroke was reduced by 39% (HR 0.61; 95% CI 0.38-0.99)
- Nonfatal MI was reduced by 26% (HR 0.74; 95% CI 0.51-1.08; not individually significant)
- New or worsening nephropathy was significantly reduced (HR 0.64; 95% CI 0.46-0.88)
- Rates of retinopathy complications were significantly higher with semaglutide (HR 1.76; 95% CI 1.11-2.78), attributed to rapid glycemic improvement
- Both semaglutide 0.5 mg and 1.0 mg weekly doses showed consistent MACE reduction
Study Design
Randomized, double-blind, placebo-controlled, cardiovascular outcomes trial. Patients with T2D aged 50+ with established CVD or CKD, or aged 60+ with CV risk factors, were randomized to subcutaneous semaglutide (0.5 mg or 1.0 mg) or volume-matched placebo weekly for 104 weeks. Primary endpoint: time to first MACE (CV death, nonfatal MI, nonfatal stroke). Designed as a noninferiority trial with pre-specified superiority testing.
Limitations
- Pre-approval regulatory CVOT; not powered for individual MACE components
- Retinopathy signal requires monitoring in clinical use, particularly in patients with pre-existing retinopathy
- Higher rates of GI adverse events led to more discontinuations in the semaglutide group
- T2D population only; CV benefit in non-diabetic obesity was subsequently addressed by SELECT
Clinical Relevance
SUSTAIN 6 was the foundational cardiovascular outcomes trial for semaglutide, establishing it as only the second GLP-1 RA (after liraglutide/LEADER) to demonstrate cardiovascular superiority in T2D. The 26% MACE reduction and nephroprotective effects positioned semaglutide as a preferred agent in T2D patients with cardiovascular disease and paved the way for the SELECT trial in obesity.
Related
#research #RCT #semaglutide #evidence-level-I