PMID-37952131 – SELECT Semaglutide Cardiovascular Outcomes in Obesity
Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine, 2023;389(24):2221-2232.
Quick Reference
| Property | Value |
|---|---|
| PMID | 37952131 |
| DOI | 10.1056/NEJMoa2307563 |
| Year | 2023 |
| Journal | New England Journal of Medicine |
| Study Type | RCT |
| Evidence Level | I |
| Sample | n=17,604 adults with overweight/obesity and established CVD, without diabetes |
| Peptide(s) Studied | Semaglutide |
Key Findings
- Semaglutide 2.4 mg weekly reduced the primary composite MACE endpoint (CV death, nonfatal MI, nonfatal stroke) by 20% vs placebo (HR 0.80; 95% CI 0.72-0.90; p<0.001)
- Mean body weight reduction of -9.39% vs -0.88% with placebo at end of trial
- Benefit observed across all three components of MACE individually
- First GLP-1 receptor agonist to demonstrate cardiovascular benefit independent of diabetes status
- Safety profile consistent with known GI side effects of GLP-1 RAs; discontinuation rate higher with semaglutide (16.6%) vs placebo (8.2%)
Study Design
Double-blind, randomized, placebo-controlled, event-driven cardiovascular outcomes trial. Participants aged 45 years or older with BMI >=27 kg/m2 and established cardiovascular disease but no diabetes were randomized 1:1 to subcutaneous semaglutide 2.4 mg weekly or placebo. Median follow-up was 39.8 months. Primary endpoint was time to first occurrence of MACE (composite of CV death, nonfatal MI, or nonfatal stroke).
Limitations
- Enrolled only patients with established CVD; generalizability to primary prevention is uncertain
- Higher discontinuation rate in the semaglutide group may introduce bias
- Unable to determine whether cardiovascular benefit is mediated by weight loss, direct GLP-1R effects, or both
- Patients with diabetes were excluded, limiting direct comparison with SUSTAIN 6 population
Clinical Relevance
SELECT is a landmark trial establishing that semaglutide reduces major cardiovascular events in overweight/obese patients without diabetes. This expands the therapeutic rationale for GLP-1 RA use beyond glycemic control and weight loss into cardiovascular risk reduction in the broader obesity population.
Related
#research #RCT #semaglutide #evidence-level-I