Outcome trial — Semaglutide 2.4 mg (Wegovy)
SELECT: trial summary, limitations and UK relevance
Semaglutide 2.4 mg weekly reduced the risk of MACE-3 compared with placebo in the studied population, demonstrating cardiovascular benefit for an anti-obesity dose of semaglutide in adults with established CVD and overweight or obesity but without diabetes. Reported hazard ratio: ~0.80 (95% CI ~0.72–0.90) per the primary NEJM publication. This is the first cardiovascular outcomes trial of an obesity-class medicine in a non-diabetic CVD population to show MACE reduction.
Key findings
Semaglutide 2.4 mg weekly reduced the risk of MACE-3 compared with placebo in the studied population, demonstrating cardiovascular benefit for an anti-obesity dose of semaglutide in adults with established CVD and overweight or obesity but without diabetes. Reported hazard ratio: ~0.80 (95% CI ~0.72–0.90) per the primary NEJM publication. This is the first cardiovascular outcomes trial of an obesity-class medicine in a non-diabetic CVD population to show MACE reduction.
Safety summary
GI adverse events were more frequent with semaglutide than placebo. Discontinuation due to adverse events was higher with semaglutide. No new major safety signals were highlighted in the primary publication beyond the established class profile.
Limitations
- Population restricted to age ≥45 with established CVD; generalisability to younger and primary-prevention populations is limited.
- MACE-3 primary endpoint does not capture all cardiovascular outcomes (e.g., heart failure events tracked separately).
- Underlying mechanism for CV benefit not definitively established (weight, glycaemic, direct vascular, anti-inflammatory pathways all plausible contributors).
UK relevance
Foundational evidence supporting consideration of semaglutide 2.4 mg in adults with overweight/obesity and pre-existing cardiovascular disease in UK clinical pathways. Informs NICE and MHRA evaluation of the cardiovascular dimension of incretin therapy beyond weight reduction.
- Does not establish benefit in primary-prevention populations without established CVD.
- Does not prove the same effect for other GLP-1 receptor agonists at other doses.
- Does not establish that weight reduction alone explains the cardiovascular benefit.
- Does not establish cardiovascular benefit for tirzepatide or retatrutide; SELECT is a semaglutide trial.
Frequently asked questions
What does the SELECT trial show?
SELECT showed that semaglutide 2.4 mg weekly reduced the risk of major adverse cardiovascular events (MACE-3: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) compared with placebo over a median follow-up of approximately 39.8 months in adults with overweight or obesity and established cardiovascular disease but without type 2 diabetes.
Does SELECT apply to people without cardiovascular disease?
No. The SELECT trial enrolled adults aged 45 or over with pre-existing cardiovascular disease. Its findings do not establish cardiovascular benefit in primary-prevention populations without established CVD, or in younger adults.
How is SELECT relevant to UK NHS prescribing?
SELECT is the primary outcome-trial evidence base for consideration of semaglutide 2.4 mg (Wegovy) in adults with overweight or obesity and established cardiovascular disease in UK clinical pathways. It informs NICE and MHRA evaluation of cardiovascular benefit beyond weight reduction alone.
Related peptide profiles
Related trials
Related conditions
Related mechanisms
Related safety signals
Sources are tagged by class. Regulatory documents, peer-reviewed publications and trial registry records are preferred. Manufacturer disclosures and conference material are accepted where peer-reviewed publication is not yet available; preprints are flagged.
- Peer-reviewed publicationLincoff AM et al., Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). NEJM 2023.
- Trial registry recordClinicalTrials.gov NCT03574597