ECO 2025: Early Clinical Benefit of Semaglutide in Adults with Overweight or Obesity and Cardiovascular Disease: A Secondary Analysis of the SELECT Trial
Introduction:
The SELECT trial previously showed that semaglutide reduced major adverse cardiovascular events (MACE) by 20% over a mean of 40 months in people with overweight/obesity and established cardiovascular disease (CVD) without diabetes. This secondary analysis aimed to explore how early these cardiovascular benefits began to emerge.
Methods:
- Design: Secondary analysis of the SELECT trial (n = 17,604), a randomized, placebo-controlled trial.
- Participants: Adults with BMI ≥27 kg/m² and CVD, but no diabetes.
- Intervention:
- Once-weekly semaglutide (titrated up to 2.4 mg by week 16) vs. placebo.
- Both groups received standard of care.
- Endpoints:
- Primary: Time to first MACE (Composite of CV death, nonfatal MI, or stroke).
- Secondary: CV death, heart failure composite, all-cause mortality.
- Analysis:
- Hazard ratios (HRs) calculated for early time intervals (0–3 and 0–6 months).
- Cumulative MACE incidence analyzed using Aalen–Johansen estimator.
Results:
|
Outcome |
Time Point |
Hazard Ratio (HR) |
95% CI |
|
MACE (overall) |
Full trial |
0.80 |
0.72 – 0.89 |
|
MACE |
0–3 months |
0.63 |
0.41 – 0.95 |
|
MACE |
0–6 months |
0.60 |
0.44 – 0.81 |
|
CV death |
0–6 months |
0.50 |
0.26 – 0.93 |
|
HF composite |
0–6 months |
0.41 |
0.24 – 0.67 |
|
All-cause mortality |
0–6 months |
0.60 |
0.36 – 1.01 |
|
Body weight reduction |
Week 4 |
−1.1% |
−1.2 to −1.1 |
|
Week 12 |
−3.6% |
−3.7 to −3.5 |
- Early separation in MACE incidence curves seen before full dose titration to 2.4 mg.
- Benefits in MACE appeared before significant weight loss occurred.
Conclusion:
Semaglutide was associated with a rapid reduction in cardiovascular risk within 3 to 6 months, including benefits in MACE, CV death, and heart failure outcomes. These effects occurred prior to meaningful weight loss or full dose escalation, suggesting early cardio-protective action. Further research is needed to uncover the underlying mechanisms.
ECO, 11-14 May 2025, Malaga, Spain
