Ozempic and Wegovy protect the heart, even without weight loss

Researchers say this discovery points to several potential ways the drug supports heart health, suggesting that its protective effects go beyond weight loss alone.

Large study confirms wide-ranging heart benefits

Published in The scalpel Funded by Novo Nordisk, the study analyzed data from 17,604 adults aged 45 and older who were overweight and had cardiovascular disease. Participants were randomly assigned to receive weekly semaglutide injections or a placebo.

Previous results from the same international research team showed that semaglutide reduced the risk of heart attacks, strokes and other major cardiac events by 20%.

In the new analysis, scientists found that these heart benefits occurred across all body types. Slightly overweight people, with a body mass index (BMI) of 27 (the average BMI among UK adults), received similar protection as participants with obesity and a much higher BMI.

Waist size plays a role but not the whole story

The reduction in cardiovascular disease risk remained largely the same regardless of how much weight participants lost during the first four and a half months of treatment. However, a reduction in waist size (waist circumference) was linked to about a third of the heart protection seen after two years of taking semaglutide.

Professor John Denfeld (UCL Institute of Cardiovascular Sciences), who led the study, explained: “Belly fat is more risky for our cardiovascular health than overall weight, and therefore it is not surprising to see a link between reduced waist size and cardiovascular benefit. However, this still leaves two-thirds of semaglutide’s heart benefits unexplained.”

He added: “These results reframe what we think this drug does. It is described as a weight-loss injection, but its benefits for the heart are not directly related to the amount of weight lost. In fact, it is a drug that directly affects heart disease and other diseases of aging.”

Implications for how the medication is used

According to Professor Denfeld, the research could change how semaglutide and similar medicines are prescribed. “You don’t have to lose a lot of weight and you don’t need to have a high BMI to get cardiovascular benefits. If your goal is to reduce cardiovascular disease, restricting its use to only a limited time and to those with the highest BMI doesn’t make sense.”

He cautioned that benefits must always be balanced with safety considerations: “Benefits must be weighed against potential side effects. Investigations into side effects are particularly important given the wide range of people this drug and other similar drugs can help.”

A broader class of drugs that help the heart

Although this study focused on semaglutide, researchers believe the same findings may apply to other drugs that act on the same hormonal system (glucagon-like peptide-1, or GLP-1).

GLP-1 medications may improve cardiovascular health by enhancing the function of the linings of blood vessels, reducing inflammation, improving blood pressure regulation, and lowering cholesterol and other fats in the bloodstream.

The analysis was based on data from the landmark SELECT trial, the largest and longest clinical trial to date looking at the effects of semaglutide on weight in people who are overweight or obese but do not have diabetes. The trial included more than 17,000 participants from around the world and was co-led by Professor Denfeld.

Semaglutide, a GLP-1 receptor agonist, mimics the body’s natural incretin hormones that help control blood sugar after meals. It was first approved for the management of type 2 diabetes.

From treating diabetes to protecting the heart

Semaglutide is the active ingredient in the medicines Wegovy and Ozempic. Following evidence from the SELECT trial, the UK Medicines Regulatory Authority has approved Wegovy for use in patients with cardiovascular disease, allowing it to be prescribed privately.

In the NHS, Wegovy is available through specialist weight loss clinics. Another GLP-1 drug, Mongaro, can be prescribed by general practitioners in England to people with a body mass index of 40 or higher (or 37.5 for those from minority ethnic backgrounds) and at least four of five conditions (type 2 diabetes, high blood pressure, cardiovascular disease, high cholesterol, and obstructive sleep apnea).

The study authors noted that most participants were male and white. They recommended that future research on GLP-1 receptor agonists include broader representation across gender and race to better understand how different populations respond to these drugs.

A preliminary analysis of the SELECT data that laid the foundation for this research was presented by Professor Denfeld and his co-authors at the European Congress on Obesity (ECO) last year.