Heart benefits of weight-loss drug extend to people with heart failure, study finds

The anti-obesity drug semaglutide could help prevent heart attacks and other major adverse cardiac events in overweight people with cardiovascular disease, whether or not they also have heart failure, according to a new study led by UCL’s Professor John Deanfield.

These findings follow previous research by the same international team, which found that weekly injections of semaglutide were linked to a 20% reduction in major adverse cardiac events (MACIs) such as heart attacks and strokes in people who were obese or overweight and had cardiovascular disease.

The new study, published in The Lancetfound similar cardiovascular benefits for a subgroup of study participants who were also judged to have heart failure (meaning their heart was not pumping blood around the body properly) by a clinician at the start of the trial.

The researchers looked at data from 4,286 people, out of a total of 17,605 people from the landmark Semaglutide and Cardiovascular Outcomes (SELECT) trial, who were randomly assigned to either semaglutide or placebo and followed 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 versus 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 from all causes.

Lead author Professor John Deanfield (UCL Institute of Cardiovascular Science) said: “Our previous SELECT analysis showed the benefits of semaglutide for people with cardiovascular disease who were obese or overweight. This new study shows that in this group, people with heart failure fared as well as people without heart failure in terms of the outcomes we measured.

“This is important because there was concern that semaglutide might be harmful to people with a type of heart failure called reduced ejection fraction, where the heart pumps less blood around the body. Our results show that the benefits of semaglutide were similar regardless of the type of heart failure.”

The study looked at data from the SELECT trial, the largest and longest clinical trial of the effects of semaglutide on weight in more than 17,000 adults who did not have diabetes but were overweight or obese. The international team leading the trial includes Professor Deanfield.

Semaglutide, a GLP-1 receptor agonist, mimics the functions of the body’s natural incretin hormones, which help lower blood sugar levels after a meal. It was initially prescribed for adults with type 2 diabetes.

Semaglutide is the active ingredient in Wegovy and Ozempic. In July, based on the results of the SELECT trial, the UK Medicines Regulatory Authority approved Wegovy as a treatment for people with cardiovascular disease, meaning it can be prescribed privately.

However, the drug is not yet recommended for this use on the NHS. Its benefits may first need to be compared with those of another new drug, SGLT2 inhibitors, a diabetes drug that also has cardiovascular benefits. (Wegovy is already available on the NHS to help with weight management and for people with type 2 diabetes.)

The exact mechanism by which semaglutide provides cardiovascular benefits is not known, but may include the drug’s positive effects 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 across all heart failure groups “suggests the potential for other, as yet unknown, benefits.”

The study compared the impact of semaglutide in 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 types of heart failure have different causes and respond differently to treatment, with preserved ejection fraction, the most common type, not responding as well to traditional treatments, resulting in a substantial unmet clinical need.

The researchers found that the clinical benefit of semaglutide was independent of the type of heart failure. It was also independent of age, sex, baseline BMI, and clinical status.

Serious adverse events were reported more frequently in the placebo group than in the semaglutide group. Treatment was discontinued more frequently in the semaglutide group, primarily due to gastrointestinal disturbances (14.7% versus 9.0% in the heart failure groups; and 17.2% versus 7.9% in the non-heart failure groups).

These results, they said, support the use of semaglutide, in addition to usual care, to reduce the risk of major adverse cardiac events in a large population of people with established atherosclerotic cardiovascular disease and overweight/obesity.

The researchers stressed that additional trials are needed to assess the impact of semaglutide on heart failure outcomes. Because SELECT was not a dedicated heart failure trial, the study results cannot be extrapolated to heart failure patients in general, they said.

In their limitations section, the authors noted that a majority of study participants were men and a large proportion of them were white. In the future, they said, trials of GLP-1 receptor agonists should examine responses by race and gender.