SELECT: semaglutide and heart attack or stroke risk without diabetes

Why this study matters

Semaglutide (Wegovy, Ozempic) had already been shown to reduce cardiovascular events in people with type 2 diabetes. SELECT asked a different question: in people with a higher body weight and existing heart disease, but no diabetes, does the medicine lower the chance of a heart attack, stroke or death from cardiovascular causes? This is the first large trial of a weight-management medicine with heart events, rather than kilograms, as the main outcome. Canadian readers with heart disease who are considering treatment often hear about it.

Who was in the study

SELECT enrolled 17,604 people: 8,803 assigned to semaglutide and 8,801 to placebo. Everyone was aged 45 or older, had pre-existing cardiovascular disease (such as a previous heart attack or stroke), and had a BMI of 27 or higher. BMI (body mass index) compares weight with height. No one had a history of diabetes.

People took the study medicine for a mean of 34.2 months and were followed for a mean of 39.8 months. The trial was multicentre, meaning it ran at many sites. The summary we reviewed does not list the countries.

What the researchers did

This was a randomized, double-blind, placebo-controlled, event-driven trial. Randomized means chance decided the treatment. Double-blind means neither participants nor study staff knew who was on the medicine. Placebo means an inactive injection. Event-driven means the trial continued until enough heart events had happened to give a reliable answer, rather than running for a fixed number of weeks.

People were assigned 1:1 to semaglutide 2.4 mg injected once a week or to placebo. The trial was designed to test superiority, meaning whether semaglutide was better than placebo. The main outcome was the time to the first of three events: death from cardiovascular causes, non-fatal heart attack, or non-fatal stroke. This combined outcome is often called MACE. Safety was also assessed.

What they found

A first major cardiovascular event occurred in 569 of 8,803 people (6.5%) in the semaglutide group and 701 of 8,801 (8.0%) in the placebo group (R32-C15).

The hazard ratio was 0.80, with a 95% confidence interval of 0.72 to 0.90. A hazard ratio compares the rate of events between groups over time; 0.80 means the rate was lower with semaglutide. The confidence interval is the range where the true value most likely lies, and because the whole range is below 1.0, the result is unlikely to be chance (P less than 0.001).

The published summary we reviewed does not report the amount of weight lost in SELECT.

Side effects and people who stopped

Adverse events led to permanent discontinuation of the study medicine in 1,461 people (16.6%) on semaglutide and 718 people (8.2%) on placebo (R32-C16). This difference was unlikely to be chance (P less than 0.001). The summary we reviewed does not break down the types of side effects. A separate prespecified safety analysis of SELECT does, and it is covered on its own page.

What this study does not tell you

• Everyone already had cardiovascular disease. The result does not show what semaglutide does for people with a higher body weight who have no heart disease.
• No one had diabetes, so the result does not apply to people with type 2 diabetes.
• Follow-up was reported in months (mean 39.8), and the summary we reviewed does not give the number of weeks or the weight change.
• SELECT results cannot be lined up against trials of other medicines, because the people, outcomes and follow-up differ.
• The trial was funded by the maker of semaglutide.
• Our data extraction relied on the abstract only, because the full text was not available to us.

What it means in Canada

SELECT is the trial most often cited when people say semaglutide protects the heart. The result applies to a specific group: adults 45 and older with existing cardiovascular disease and a BMI of 27 or higher, without diabetes. Whether it is used or covered for this purpose in Canada is a separate question. See semaglutide in Canada and public drug coverage by province.

Related reading

Other studies in this library that bear on the same question.

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