SELECT: semaglutide and cardiovascular events in obesity without diabetes

SELECT is the trial that moved semaglutide from "a weight drug" to "a drug with a cardiovascular indication" in people who do not have diabetes. Its primary endpoint is events, not kilograms.

What the trial asked

Whether semaglutide 2.4 mg reduces major adverse cardiovascular events in people with overweight or obesity and established cardiovascular disease, in the absence of diabetes.

Design

Multicentre, double-blind, randomised 1:1, placebo-controlled, event-driven superiority trial. Once-weekly semaglutide 2.4 mg versus placebo. Primary endpoint: a composite of death from cardiovascular causes, nonfatal myocardial infarction or nonfatal stroke, analysed as time to first event.

"Event-driven" means the trial ran until a prespecified number of primary events had accumulated rather than for a fixed number of weeks. Mean exposure to trial product was 34.2 months (SD 13.7); mean follow-up 39.8 months (SD 9.4).

Who was enrolled

17,604 patients aged 45 or older with pre-existing cardiovascular disease and a BMI of 27 or greater, with no history of diabetes. 8803 were assigned to semaglutide and 8801 to placebo.

Primary endpoint and result

A primary cardiovascular event occurred in 569 of 8803 (6.5 percent) on semaglutide and 701 of 8801 (8.0 percent) on placebo. Hazard ratio 0.80 (95% CI 0.72 to 0.90; P less than 0.001).

In plain terms: over roughly three and a third years, 1.5 fewer people in every 100 had a heart attack, stroke or cardiovascular death on semaglutide than on placebo. The relative reduction is 20 percent; the absolute reduction is 1.5 percentage points.

Key secondary results

The abstract does not report the components of the composite individually, weight change, or the other confirmatory secondary endpoints. They are in the full paper and are not repeated here.

Adverse events and discontinuation

Adverse events leading to permanent discontinuation of the trial product occurred in 1461 patients (16.6 percent) on semaglutide and 718 (8.2 percent) on placebo (P less than 0.001). The abstract does not itemise the events.

Funding and registration

Novo Nordisk. ClinicalTrials.gov NCT03574597.

What this trial does not show

• Everyone had established cardiovascular disease. The result is secondary prevention. It does not tell you what semaglutide does for someone with obesity and no cardiovascular history.
• It does not tell you whether the benefit came through weight loss, through a direct vascular effect, or both. The abstract does not report weight change, which is the single most common misquotation of this trial.
• A 20 percent relative risk reduction sounds larger than a 1.5 point absolute reduction. Both are the same result; keep them together.
• Discontinuation for adverse events was twice as common on semaglutide. That number rarely travels with the headline.

Where the numbers come from

PubMed abstract of the primary paper (PubMed 37952131), fetched 4 September 2026. The diabetes cardiovascular trials are SUSTAIN-6 (injectable) and PIONEER 6 (oral). See also the how to read a GLP-1 trial guide on relative versus absolute risk.