The researchers examined data from 4,286 patients — out of a total of 17,605 in the landmark Semaglutide and Cardiovascular Outcomes (SELECT) experiment who were randomly allocated either semaglutide or a placebo and were followed up for an average of more than three years.
According to a recent study conducted by UCL’s Professor John Deanfield, the anti-obesity medicine semaglutide may help to avoid heart attacks and other severe adverse cardiac events in overweight adults with cardiovascular disease, regardless of whether they also have heart failure.
The results follow previous research from the same international team finding that weekly injections of semaglutide were linked to a 20% reduction in major adverse cardiac events (MACE) such as heart attacks and strokes for people with obesity or who were overweight and had cardiovascular disease.
The latest study, published in The Lancet, discovered similar cardiovascular advantages for a subset of study participants who were also diagnosed with heart failure (i.e., their hearts did not properly pump blood around the body) by a clinician at the beginning of the experiment. The researchers examined data from 4,286 patients — out of a total of 17,605 in the landmark Semaglutide and Cardiovascular Outcomes (SELECT) experiment who were randomly allocated either semaglutide or a placebo and were followed up for an average of more than three years.
They found that semaglutide was linked to a 28% reduction in major adverse cardiac events (12.3% in the placebo group had such events compared to 9.1% in the semaglutide group), as well as a 24% reduction in cardiovascular disease-related deaths for this subgroup of people with pre-existing heart failure, and a 19% reduction in deaths of any cause.
Our previous SELECT research demonstrated the benefits of semaglutide for persons with cardiovascular disease who were obese or overweight. According to this new study, those with heart failure performed equally well as those without in terms of the outcomes we measured.
Professor John Deanfield
Lead author Professor John Deanfield (UCL Institute of Cardiovascular Science) stated, “Our previous SELECT research demonstrated the benefits of semaglutide for persons with cardiovascular disease who were obese or overweight. According to this new study, those with heart failure performed equally well as those without in terms of the outcomes we measured.”
“This is significant because there were worries that semaglutide could be harmful* to persons with a kind of heart failure known as decreased ejection fraction, in which the heart pumps less blood across the body. Our data suggest that semaglutide had equal benefits independent of the kind of heart failure.”
The study looked at data from the landmark SELECT trial — the largest and longest clinical trial of the effects of semaglutide on weight in over 17,000 adults who did not have diabetes but who were overweight or had obesity. The international team that runs the trial includes Professor Deanfield.
Semaglutide, a GLP-1 receptor agonist, simulates the functions of the body’s natural incretin hormones, which help to lower blood sugar levels after a meal. It was initially prescribed for adults with type 2 diabetes.
Semaglutide is the active ingredient in both Wegovy and Ozempic. Wegovy was approved as a treatment for cardiovascular illness by the UK drugs authority in July, based on findings from the SELECT study, allowing it to be prescribed privately. However, the medicine is not yet prescribed for this use by the NHS. Its benefits may need to be compared to those of another new pharmaceutical, SGLT2 inhibitors, a diabetes therapy that has been shown to have cardiovascular benefits. (Wegovy is currently available on the NHS to assist with weight management and type 2 diabetes.)
The exact mechanism through which semaglutide delivers cardiovascular benefits is not known, but may include the drug’s positive impacts on blood sugar, blood pressure, and inflammation, as well as direct effects on the heart muscle and blood vessels.
The researchers said the reduction in all-cause mortality in all heart failure groups “suggests the potential for other, as yet unknown, benefits.”
The study compared the impact of semaglutide for people with two types of heart failure: preserved ejection fraction, where the heart pumps blood normally but is too stiff to fill properly, and reduced ejection fraction. These two heart failure types have different causes and respond to treatment differently, with preserved ejection fraction, the most common type, not responding so well to traditional treatments, leading to considerable unmet clinical need.
The researchers discovered that the therapeutic benefit of semaglutide was independent of the kind of heart failure. It was also discovered to be independent of age, gender, starting BMI, and clinical status. Serious adverse events were recorded more frequently in the placebo group compared to the semaglutide group. Treatment was terminated more frequently in the semaglutide group, mostly due to gastrointestinal problems (14.7% vs 9.0% in the heart failure groups; 17.2% vs 7.9% in the non-heart failure groups).
These findings, they added, justified the use of semaglutide, in addition to standard therapy, to lower the risk of significant adverse cardiac events in a large group of adults with established atherosclerotic cardiovascular disease and obesity.
The researchers stated that more studies were needed to assess the effect of semaglutide on heart failure-related outcomes. Because SELECT was not a specific heart failure trial, the study outcomes cannot be extended to all patients with heart failure, they noted.
In their section on limitations, the authors highlighted that the majority of research participants were men, with a high proportion being Caucasian. They recommended that future GLP-1 receptor agonist trials look at results based on ethnicity and gender.
