Why Semaglutide's Heart Protection May Go Beyond Weight Loss

Weight loss can support heart health, but that may not explain all of semaglutide’s cardiovascular benefits.

According to new research, the drug’s ability to cut the risk of heart attack, stroke and cardiovascular death cannot be fully accounted for by weight loss or other familiar risk factors.

The findings, published in the European Heart Journal, come from researchers at the University of Edinburgh. Their analysis used data from the SELECT trial, which followed 17,604 adults with overweight or obesity and established cardiovascular disease, but no diabetes.

Semaglutide is part of a class of medicines that mimic a natural hormone involved in appetite and blood sugar regulation. Originally developed for diabetes, these drugs are now also widely used to treat obesity. Earlier SELECT results showed that semaglutide reduced major cardiovascular events by about 20% compared with placebo.

The new analysis looked at why that happened. Researchers examined changes in body weight, waist circumference, blood pressure and cholesterol, along with markers linked to blood sugar, inflammation and kidney function.

Although people taking semaglutide lost weight and improved in several health measures, the measured factors appeared to explain only about half of the reduction in cardiovascular risk.

That leaves a key question unresolved. Semaglutide may influence the cardiovascular system in other ways, possibly by lowering inflammation or acting more directly on blood vessels or heart muscle. Those possibilities will need further study.

The researchers also cautioned that this kind of analysis cannot separate every cause of the benefit with precision. Data collection during the trial was affected by the COVID-19 pandemic, and some participants may have lost weight for reasons unrelated to semaglutide.

An accompanying editorial said scientists still do not fully understand how this drug class produces such wide-ranging benefits.

The study matters because it challenges the simple view that semaglutide protects the heart mainly by helping patients lose weight. Still, it does not prove what explains the remaining benefit, so more research is needed to identify the biological mechanisms involved.

Source: University of Edinburgh.