The study analyzed data from 4,286 participants who were part of the significant Semaglutide and Cardiovascular Outcomes (SELECT) trial, which included a total of 17,605 individuals randomly assigned to receive either semaglutide or a placebo. The participants in this analysis were monitored for an average duration of over three years.
According to a recent study led by UCL’s Professor John Deanfield, the anti-obesity medication semaglutide might aid in reducing the risk of heart attacks and other serious cardiac issues in overweight individuals suffering from cardiovascular disease, regardless of whether or not they experience heart failure.
These findings follow earlier research from the same international team, which indicated that semaglutide, administered weekly via injections, was associated with a 20% decrease in major adverse cardiac events (MACE), including heart attacks and strokes, in individuals with obesity or who were overweight and experienced cardiovascular disease.
Published in The Lancet, the new study observed similar benefits for a subgroup of patients diagnosed with heart failure (where the heart struggles to pump blood effectively) at the beginning of the trial.
The researchers focused on data from 4,286 participants in the SELECT trial, where they were randomly assigned to receive either semaglutide or a placebo. The follow-up period averaged more than three years.
Results showed that semaglutide was associated with a 28% decrease in major adverse cardiac events (with 12.3% of the placebo group experiencing such events compared to 9.1% in the semaglutide group), a 24% reduction in cardiovascular-related fatalities for those with pre-existing heart failure, and a 19% decrease in overall mortality.
Lead author Professor John Deanfield from the UCL Institute of Cardiovascular Science remarked: “Our previous SELECT analysis highlighted the positive effects of semaglutide on individuals with cardiovascular disease who were either overweight or had obesity. This new analysis indicates that, within this specific group, individuals with heart failure experienced similar outcomes to those without heart failure.”
“This finding is significant, as there were worries that semaglutide might be detrimental* for people with a kind of heart failure termed reduced ejection fraction, which means the heart pumps less blood. Our results indicate that semaglutide provides benefits regardless of the type of heart failure.”
The research drew on data from the SELECT trial, recognized as the largest and longest investigation into semaglutide’s effects on weight among more than 17,000 non-diabetic adults who were overweight or had obesity. The international team conducting the trial includes Professor Deanfield.
Semaglutide, categorized as a GLP-1 receptor agonist, mimics the actions of the body’s natural incretin hormones, which aid in lowering blood sugar after meals. Initially, it was prescribed for adults dealing with type 2 diabetes.
Semaglutide is the active component in Wegovy and Ozempic. In July, following findings from the SELECT trial, the UK medicines regulator authorized Wegovy as a treatment for individuals with cardiovascular disease, enabling private prescriptions.
Nonetheless, this drug is not yet recommended by the NHS for this purpose. Before it can be endorsed, its advantages may need to be compared with another new medication, SGLT2 inhibitors, a diabetes treatment that has also been found beneficial for cardiovascular health. (Wegovy is currently available on the NHS for weight management and for patients with type 2 diabetes.)
The precise way semaglutide provides cardiovascular benefits remains unclear, but it could involve positive effects on blood sugar levels, blood pressure, inflammation, as well as direct influences on cardiac muscle and blood vessels.
The researchers suggested that the reduction in overall mortality across all heart failure categories “hints at possible additional, currently unknown advantages.”
The study compared the effects of semaglutide for patients with two forms of heart failure: preserved ejection fraction, where the heart pumps normally but is too rigid to fill adequately, and reduced ejection fraction. These two types of heart failure arise from distinct causes and respond differently to treatments, with preserved ejection fraction being the most common yet less responsive to conventional therapies, leading to significant unmet medical needs.
Findings demonstrated that the clinical advantages of semaglutide were unrelated to the type of heart failure. It was also determined to be independent of age, sex, initial BMI, and medical condition. Serious side effects were reported more commonly in the placebo group than in the semaglutide group. Treatment interruptions were more frequent in the semaglutide cohort, mainly due to gastrointestinal issues (14.7% vs. 9.0% in heart failure groups; and 17.2% vs. 7.9% in non-heart failure groups).
The authors emphasized the importance of semaglutide as an adjunct to standard care for decreasing the likelihood of major adverse cardiac events in a diverse population suffering from established atherosclerotic cardiovascular disease along with overweight or obesity.
They acknowledged the necessity for further trials to assess the effect of semaglutide on outcomes related to heart failure. Since SELECT was not explicitly a heart failure trial, the results may not be applicable to all heart failure patients.
In addressing limitations, the authors noted that a majority of participants were male and a significant portion were white. In upcoming studies, they suggested examining the responses to GLP-1 receptor agonists based on ethnicity and gender.
This study received funding from Novo Nordisk.
*Previous small studies suggested that a similar medication, liraglutide, could potentially be harmful to individuals with reduced ejection fraction heart failure.
