# SELECT: what the trial showed

Canonical page: https://cliniatlas.com/trials/select/

In 17,604 adults with established cardiovascular disease and a BMI of 27 or more but no diabetes, once-weekly semaglutide 2.4 mg reduced cardiovascular death, nonfatal MI, or nonfatal stroke from 8.0% to 6.5% over a mean follow-up of 39.8 months.

**Main cited publication:** Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine (2023). PMID 37952131. https://pubmed.ncbi.nlm.nih.gov/37952131/

## At a glance

- Design: Multicentre, randomised, double-blind, placebo-controlled, event-driven superiority trial
- Population: 17,604 adults aged 45 or older with pre-existing cardiovascular disease and a BMI of 27 or more, without a history of diabetes
- Intervention: Semaglutide 2.4 mg subcutaneously once weekly
- Comparator: Placebo
- Follow-up: Mean 39.8 months (mean exposure 34.2 months)
- Registration: NCT03574597
- Funding: Novo Nordisk

## Primary outcome

Composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (time to first event).

- Semaglutide 2.4 mg subcutaneously once weekly: 6.5% (569 of 8,803)
- Placebo: 8.0% (701 of 8,801)
- Effect: Hazard ratio 0.80 (95% CI 0.72 to 0.90), P<0.001

## Key findings

- The absolute reduction in the primary endpoint was about 1.5 percentage points over roughly three years, or one event prevented per 67 patients treated.
- This was the first trial to show that a GLP-1 receptor agonist reduces major cardiovascular events in people with overweight or obesity who do not have diabetes.
- The benefit appeared early, before the full weight loss had developed, which has fuelled debate about how much of the effect is weight-mediated.

## Harms and safety

- Adverse events leading to permanent discontinuation were more frequent with semaglutide: 16.6% versus 8.2%, mostly gastrointestinal.

## Limitations

- A secondary prevention population with established cardiovascular disease; the result does not speak to primary prevention in obesity.
- The trial was not designed to separate weight loss from other mechanisms.
- Industry funded; the treatment is costly and requires continuous use.

## Where it sits in guidelines

SELECT led to label updates describing cardiovascular risk reduction for semaglutide 2.4 mg, first in the United States in March 2024 and subsequently in the EU. Check the current SmPC for the authorised wording in your country.

## CliniAtlas answers that use this trial

- https://cliniatlas.com/evidence/semaglutide-weight-loss-adults-overweight-obesity/
- https://cliniatlas.com/evidence/glp1-receptor-agonists-cardiovascular-events-type-2-diabetes/

Ask about this trial against live sources (free, no sign-in): https://cliniatlas.com/?q=What%20did%20the%20SELECT%20trial%20show%20and%20how%20should%20it%20be%20interpreted%3F

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