SELECT safety analysis: semaglutide side effects in heart disease

Why this study matters

SELECT was a large, multi-year randomized trial of semaglutide (Wegovy, Ozempic) at the weight-management dose, in people with heart disease. That makes it an important place to look for side effects that only show up in big groups or over years. The main SELECT paper reported only the headline discontinuation figures. This paper is the planned, detailed safety report. For Canadian readers weighing the medicine's risks, it gives a fuller long-term safety picture from this trial.

Who was in the study

The analysis covered all 17,604 SELECT participants: 8,803 assigned to semaglutide and 8,801 to placebo. Everyone had overweight or obesity and established cardiovascular disease, and no one had diabetes. Safety was summarized for everyone randomized, during the time they were in the trial, regardless of whether they stayed on the medicine or changed other medications. The follow-up period in weeks was not extracted.

What the researchers did

SELECT was a randomized, double-blind, placebo-controlled trial. Randomized means chance decided the treatment. Double-blind means neither participants nor staff knew who was on the medicine. Placebo means an inactive injection. People injected semaglutide 2.4 mg or placebo once a week.

This is a prespecified safety analysis, meaning the safety questions were planned before the trial. Safety data collection was targeted. It focused on serious adverse events, all adverse events that led to permanent discontinuation of treatment (whether serious or not), and a set of prespecified adverse events of special interest. A serious adverse event is one that causes death, is life-threatening, requires a hospital stay, or causes lasting harm. Mild side effects that did not lead to stopping were not collected in full.

What they found

Serious adverse events were less common with semaglutide than placebo: 33.4% versus 36.4% (P less than 0.001) (R32-C27). The difference was driven mainly by fewer cardiac disorders (11.5% versus 13.5%; P less than 0.001), which fits with the trial's main heart result.

Adverse events leading to discontinuation were more common with semaglutide (16.6% versus 8.2%; P less than 0.001), a difference driven by stomach and gut problems (10.0% versus 2.0%). Stopping because of a serious event was similar in both groups (3.6% versus 4.1%).

Gallbladder disorders were slightly more frequent with semaglutide (2.8% versus 2.3%; P = 0.04), mainly gallstones (1.4% versus 1.1%), while cholecystitis was the same in both groups (0.6% versus 0.6%) (R32-C28). Serious suicide or self-injury events were rare and balanced (0.11% in both groups).

The authors concluded that the long-term safety profile was consistent with earlier semaglutide studies and that no new safety concerns were identified.

Side effects and people who stopped

This whole page is about side effects. In short: fewer serious events overall with semaglutide, mostly because of fewer cardiac events; more people stopped because of side effects, mostly gut-related; slightly more gallbladder problems; no difference in serious suicide or self-injury events.

What this study does not tell you

• Safety collection was targeted at serious events, discontinuations and special-interest events. It is not a complete count of every mild side effect.
• No signal in a trial is not proof that a rare risk does not exist.
• This is the same group of people as the main SELECT paper, not new participants, so it is not additional evidence about how many people are affected.
• Everyone had cardiovascular disease and no diabetes, so the balance of risks may differ in other groups.
• The summary we reviewed does not state the funding source. The authors reported multiple industry consulting and research relationships, including with Novo Nordisk, the maker of semaglutide.

What it means in Canada

This is a detailed long-term safety report from a semaglutide weight-management trial. It supports the common pattern: gut side effects are the main reason people stop, and gallbladder problems are slightly more frequent. For how the medicine is used and monitored here, 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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