Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial
Authors' conclusion
The cardioprotective effects of semaglutide were independent of baseline adiposity and weight loss and had only a small association with waist circumference, suggesting some mechanisms for benefit beyond adiposity reduction.
Study context
- Population
- Patients aged ≥45 years with BMI ≥27 kg/m², CVD and without diabetes
- Participants
- 17,604 patients
- Comparison
- Semaglutide vs Placebo
- Primary endpoint
- Time to first MACE (CV death, non-fatal MI or non-fatal stroke) by baseline adiposity and adiposity changes
Methodological details41 countries (804 sites)
- 41 countries (804 sites)
Primary result
As reported in the abstract
MACE per 5 kg lower / 5 cm smaller baseline bodyweight / waist circumference (linear trend)
Hazard ratio (95% CI)P value
Semaglutideper 5 kg lower baseline bodyweight
0.96(0.94–0.99)
P = 0.001Semaglutideper 5 cm smaller baseline waist circumference
0.96(0.93–0.99)
P = 0.004Placeboper 5 cm smaller baseline waist circumference
0.96(0.94–0.99)
P = 0.007Placeboper 5 kg lower baseline bodyweight
0.99(0.97–1.01)
P = 0.28Each row per its own increment, as printed
Further findings
Adiposity change and subsequent major adverse cardiovascular events (MACE) · week 20 and week 104
- Semaglutide: no linear trend linking weight loss at week 20 to subsequent MACE risk
- Semaglutide: greater waist circumference reduction at week 20 associated with lower subsequent MACE risk
- Semaglutide: waist circumference reduction by week 104 associated with lower in-trial MACE risk
- Placebo: weight loss paradoxically associated with increased MACE risk
Proportion of MACE benefit mediated through waist circumference reduction
- Estimated share of observed MACE benefit mediated through waist circumference reduction
- 33%
- HR after adjustment for time-varying changes in waist circumference
- 0.86 (95% CI 0.77-0.97)
Original publication
Semaglutide and cardiovascular outcomes by baseline and changes in adiposity measurements: a prespecified analysis of the SELECT trial. Lancet. Published 22 October 2025. doi:10.
Summarised from the published abstract; every number is checked against it