Semaglutide’s heart health benefits not solely explained by weight loss, trial finds

A new study has found that losing weight through the GLP-1 drug semaglutide may not be the sole reason for improvements in cardiovascular health linked to the medication. The researchers suggest semaglutide as a potential treatment for cardiovascular diseases. 

The scientists argue that semaglutide may work to reduce heart disease through a mechanism other than weight loss and reduced waist circumference alone.

Study lead Helen Colhoun, professor at the University of Edinburgh, UK, says: “Several major trials have established that GLP-1 receptor agonists reduce serious cardiovascular disease, primarily in people with type 2 diabetes.”

The study was based on patients taking part in a clinical trial called Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT).

“SELECT was the first trial to show that these drugs can also lower cardiovascular disease in people who did not have diabetes. In this study, we analyzed data from the trial to ascertain whether the reductions in known cardiovascular risk factors that we saw in the trial could fully account for the reduction in heart disease,” adds Colhoun.

Semaglutide for cardiovascular health?

Published in the European Heart Journal, the study included participants above 45 years old with a body mass index above 27. Half of the participants, 17,604, were treated with semaglutide, and the other half received a placebo.

In the 24-month trial, the researchers analyzed changes in blood pressure, body weight, and waist circumference. They also looked at blood tests for cholesterol, diabetes, inflammation, and kidney function. This information was used to compare rates of cardiovascular disease, including heart attack, stroke, and fatal incidents from the disease.

The study found that the participants who received semaglutide had improved blood test results, lost weight, and reduced waist measurements. When investigating these factors separately and combined, the researchers could not account for the 20% decreased rates in heart disease among the patients receiving the GLP-1 medication.

Further investigations needed

Colhoun says the analyses could not, with any certainty, fully ascribe the effects of semaglutide on cardiovascular disease to known risk factors.

The study found that the participants who received semaglutide had improved blood test results, lost weight, and reduced waist measurements.“Whether we combine all risk factors together or look at some subsets of the risk factors, no more than half of the reduction in heart disease could be explained by the changes in these risk factors,” she says. “These results suggest that semaglutide should be considered as a cardiovascular disease reduction drug and not just as a weight loss drug.”

She says that apart from weight loss, it is still unknown how else semaglutide could be preventing heart disease, but many other mechanisms have been proposed. 

“These include anti-inflammatory effects not fully captured by the risk factors measured in the trial, and other direct effects on the heart muscle or on the lining of blood vessels. We need more research to fully explore other potential mechanisms of how semaglutide reduces cardiovascular disease.”

The study authors also note that the trial included patients being treated for COVID-19, which may have impacted the data collection. There might have also been other explanations for some of the participants losing weight, beyond the semaglutide alone. 

The researchers conclude that the analysis could not explain the full effects of semaglutide on cardiovascular health, highlighting the need for further investigations of potential additional biomarkers and mediators of semaglutide’s cardioprotective effects.