Recent findings from the SELECT clinical trial showed that semaglutide reduces cardiovascular events by 20% in adults with overweight or obesity and established cardiovascular disease who do not have diabetes.
Researchers reported the results during the American Heart Association Scientific Sessions 2023, and the study was simultaneously published in the New England Journal of Medicine.
Semaglutide and Weight Management
Semaglutide is widely prescribed for adults with type 2 diabetes. It is also approved for chronic weight management in adults with obesity or overweight who have at least one weight-related health condition.
In the SELECT trial, participants treated with semaglutide achieved an average body weight reduction of 9.4%. Researchers also observed improvements in several cardiovascular risk factors.
SELECT Trial Design and Participants
The SELECT trial enrolled more than 17,000 participants from 41 countries between October 2018 and June 2023.
Eligible participants were:
- 45 years of age or older
- Living with overweight or obesity
- Diagnosed with pre-existing cardiovascular disease
- Without a history of diabetes
Participants received either once-weekly semaglutide 2.4 mg injections or placebo and were followed for an average of 40 months.
Cardiovascular Benefits Observed
Researchers found that semaglutide outperformed placebo in reducing the combined risk of:
- Cardiovascular death
- Nonfatal heart attack
- Nonfatal stroke
The primary cardiovascular outcome occurred in 6.5% of patients receiving semaglutide compared with 8.0% of those receiving placebo, representing a 20% reduction in relative risk.
The benefits remained consistent across different age groups, genders, ethnic backgrounds, and baseline body weights.
Additional Effects Beyond Weight Loss
Although semaglutide supports weight reduction primarily through appetite regulation, researchers believe additional mechanisms may contribute to cardiovascular protection.
Potential benefits include:
- Improved glucose control
- Lower blood pressure
- Reduced cholesterol levels
- Decreased inflammation
- Positive effects on blood vessels and heart function
These combined effects may help explain the cardiovascular outcomes observed during the study.
Safety Findings
Researchers reported no unexpected safety concerns during the trial.
The most common reasons for treatment discontinuation were gastrointestinal symptoms such as:
- Nausea
- Diarrhea
These effects are commonly associated with GLP-1 receptor agonists, especially during dose escalation.
Investigators observed a slightly higher incidence of gallbladder disorders in the semaglutide group compared with placebo. However, semaglutide was not associated with increased risks of:
- Severe gastrointestinal disorders
- Pancreatitis
- Psychiatric disorders
- Kidney injury
Study Limitations
The study included only individuals with established cardiovascular disease.
As a result, researchers did not evaluate whether semaglutide could prevent first-time cardiovascular events in adults with overweight or obesity who have no previous history of cardiovascular disease.
Conclusion
The SELECT trial demonstrated that semaglutide reduces cardiovascular events in adults with overweight or obesity and established cardiovascular disease who do not have diabetes.
The findings provide important evidence supporting the role of semaglutide in cardiovascular risk reduction while also highlighting its established benefits in weight management and metabolic health.