Semaglutide appears to protect the heart regardless of how much weight people lose. The discovery suggests the drug directly improves cardiovascular health, not just body weight. Credit: Shutterstock

Semaglutide may safeguard the heart even without significant weight loss.

A new study led by a researcher at University College London (UCL) suggests that the anti-obesity drug semaglutide may reduce the risk of heart attacks and other serious cardiac events even when people lose little or no weight while taking it.

According to the researchers, the results indicate that the medication supports heart health through several pathways, rather than working only by helping people lose weight.

Large Clinical Study Shows Consistent Benefits

The research, published in the Lancet journal and funded by Novo Nordisk, analyzed data from 17,604 adults aged 45 and older who were overweight and had cardiovascular disease. Participants were randomly assigned to receive weekly injections of either semaglutide or a placebo.

Previous analysis^[1] by the same international research team showed that semaglutide lowered the risk of heart attacks, strokes, and other major cardiovascular events by 20% in this population.

In the latest analysis, the researchers found that this reduction in risk was similar regardless of how much participants weighed at the beginning of the study. People who were only slightly overweight, with a body mass index (BMI) of 27 (the average BMI for adults in the UK), experienced comparable heart benefits to those with obesity and much higher BMIs.

Waist Size Matters, but It Is Not the Whole Explanation

Heart protection also appeared largely unrelated to how much weight participants lost during the first four and a half months of treatment. However, the study did find a connection between reduced waist size (the reduction in waist circumference) and improved cardiovascular outcomes. This reduction in abdominal fat explained about one third of semaglutide’s protective effect on the heart after two years.

Professor John Deanfield (UCL Institute of Cardiovascular Science), the study’s lead author, said: “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.

“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 ageing.

“This work has implications for how semaglutide is used in clinical practice. 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.

“At the same time, 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.”

What This Means for Other GLP-1 Drugs

Although the analysis focused on semaglutide, the researchers believe the findings are likely relevant to other ‘weight loss’ medications that act on the same hormone (glucagon-like peptide-1, or GLP-1).

They noted that GLP-1 drugs may support cardiovascular health by improving the function of blood vessel linings, lowering inflammation, helping regulate blood pressure, and reducing lipid levels (levels of cholesterols and other fats in the bloodstream).

Insights From the SELECT Trial

The study drew on data from the landmark SELECT trial – the largest and longest clinical trial examining the effects of semaglutide on weight in more than 17,000 adults who did not have diabetes but were overweight or had obesity. Professor Deanfield is part of the international team overseeing the trial.

Semaglutide is a GLP-1 receptor agonist that mimics the action of the body’s natural incretin hormones, which help control blood sugar levels after meals. It was originally prescribed for adults with type 2 diabetes.

From Diabetes Treatment to Broader Use

Semaglutide is the active ingredient in Wegovy and Ozempic. Last year, based on evidence from the SELECT trial, the UK medicines regulator approved Wegovy for people with cardiovascular disease, allowing it to be prescribed privately.

Within the NHS, Wegovy is offered for weight loss through specialist weight management clinics. Another GLP-1 agonist, Mounjaro, is prescribed by general practitioners in England for people with a BMI of 40 or higher (or 37.5 if from a minority ethnic background) who also have four out of five conditions (type 2 diabetes, high blood pressure, heart and vascular disease, high cholesterol, and obstructive sleep apnoea).

Study Limitations and Future Research

The authors noted several limitations, including that most study participants were male and a large proportion were white. They emphasized that future GLP-1 receptor agonist trials should examine differences in response by sex and ethnicity.

Notes

1. The preliminary analysis of SELECT data that formed the foundation of this study was presented by Professor Deanfield and his co-authors at the European Congress on Obesity (ECO) last year.

Reference: “Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes” by A. Michael Lincoff, Kirstine Brown-Frandsen, Helen M. Colhoun, John Deanfield, Scott S. Emerson, Sille Esbjerg, Søren Hardt-Lindberg, G. Kees Hovingh, Steven E. Kahn, Robert F. Kushner, Ildiko Lingvay, Tugce K. Oral, Marie M. Michelsen, Jorge Plutzky, Christoffer W. Tornøe and Donna H. Ryan, 13 December 2023, New England Journal of Medicine.
DOI: 10.1056/NEJMoa2307563

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