Ozempic and Wegovy protect the heart, even without weight loss

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

Large Study Confirms Broad Heart Benefits

Published in The Lancet and 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 either weekly semaglutide injections or a placebo.

Earlier results from the same international research team showed that semaglutide lowered 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. People who were only slightly overweight, with a body mass index (BMI) of 27 (the average BMI among UK adults), experienced similar protection as participants with obesity and much higher BMIs.

Waist Size Plays a Role but Not the Whole Story

The reduction in cardiovascular risk remained largely the same no matter how much weight participants lost during the first four and a half months of treatment. However, a decrease in waist size (waist circumference) was linked to about one-third of the heart protection seen after two years on semaglutide.

Professor John Deanfield (UCL Institute of Cardiovascular Science), who led the study, explained: "Abdominal fat is more dangerous for our cardiovascular health than overall weight and therefore it is not surprising to see a link between reduction in waist size and cardiovascular benefit. However, this still leaves two thirds of the heart benefits of semaglutide unexplained."

He added, "These findings reframe what we think this medication is doing. It is labelled as a weight loss jab 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 Drug Is Used

According to Professor Deanfield, the research could change how semaglutide and similar drugs are prescribed. "You don't have to lose a lot of weight and you don't need a high BMI to gain cardiovascular benefit. If your aim is to reduce cardiovascular disease, restricting its use to a limited time only and for those with the highest BMIs doesn't make sense."

He cautioned that benefits should always be balanced with safety considerations: "The benefits need to be weighed against potential side effects. Investigations of side effects become especially important given the broad range of people this medicine and others like it could help."

A Broader Class of Heart-Helping Drugs

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

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

The analysis drew on data from the landmark SELECT trial, which is the largest and longest clinical trial to date investigating semaglutide's effects on weight in people who were overweight or obese but did not have diabetes. The trial included more than 17,000 participants worldwide and was co-led by Professor Deanfield.

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 managing type 2 diabetes.

From Diabetes Treatment to Heart Protection

Semaglutide is the active ingredient in the medications Wegovy and Ozempic. Following evidence from the SELECT trial, the UK's medicines regulator approved Wegovy for use in patients with cardiovascular disease, allowing it to be prescribed privately.

On the NHS, Wegovy is available through specialist weight management clinics for weight loss. Another GLP-1 drug, Mounjaro, can be prescribed by general practitioners in England for people with a BMI of 40 or above (or 37.5 for those from minority ethnic backgrounds) and at least four of five conditions (type 2 diabetes, high blood pressure, heart and vascular 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 sex and ethnicity to better understand how different populations respond to these medications.

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