Prevention & lipidsSecondary analysis
Semaglutide and cardiovascular risk reduction: a mediation analysis of the SELECT trial
- Secondary analysis of the SELECT randomised trial
- mediation analysis
- Vansteelandt repeated regression method (counterfactual approach)
Authors' conclusion
Mediation analyses could not fully ascribe the effects of semaglutide on MACE to known risk factors in SELECT with any certainty.
Study context
- Population
- Adults with pre-existing CVD and BMI ≥27 kg/m² without diabetes
- Comparison
- Semaglutide vs placebo
- Primary endpoint
- % mediation of major adverse cardiovascular events (MACE) risk reduction by changes in body weight, waist circumference, hsCRP, HbA1c, lipids, BP, eGFR and urinary albumin-to-creatinine ratio
- Follow-up
- Randomization to 24 months
Primary result
As reported in the abstract
% mediation of MACE risk reduction
- Waist circumference
- 64.0% (95% CI 27.5, 179.6)
- High-sensitivity C-reactive protein (hsCRP) (17.9, 110.5)
- 42.1%
- HbA1c (−20.7, 120.5)
- 29.0%
- Body weight (−33.0, 110.7)
- 19.5%
- Joint mediation, all potential mediators combined
- 31.4% (95% CI −30.1, 143.6)
- All variables other than body weight and waist circumference
- 46.0% (95% CI −6.0, 161.0)
Further findings
Potential mediators
- Semaglutide significantly improved all potential mediators investigated
- P < 0.05
Original publication
Semaglutide and cardiovascular risk reduction: a mediation analysis of the SELECT trial. Eur Heart J. Published 23 September 2026. doi:10.1093/eurheartj/ehag524
Summarised from the published abstract; every number is checked against it