Wegovy, an injectable prescription weight loss drug, can produce effective results that help patients keep weight off for up to four years, a new study suggests. The drug may also offer heart protection benefits for overweight and obese patients who had heart disease before starting the treatment.

The drug, which is developed by Novo Nordisk, a global healthcare company based in Denmark, is based on a human hormone called glucagon-like peptide 1 (GLP-1), which plays a role in regulating our appetites and our blood sugar levels. In recent years, various studies have explored the role GLP-1 agonists, drugs that mimic the effects of this hormone, can have on obesity and conditions like type-2 diabetes.

Wegovy’s active ingredient, a molecule called semaglutide, is another example of a GLP-1 mimic. It acts on the parts of our brains associated with hunger and fullness. Semaglutide also lowers blood sugar levels by promoting the release of insulin when levels are already high.

Wegovy has been approved by the US Food and Drug Administration and has been approved by the UK's NHS to be used alongside diet and physical activity designed to manage excess weight and obesity.

The new analysis comes from the longest clinical trial of the drug to date, the results of which were presented at the European Congress on Obesity in Venice this week.

The results add to the growing body of evidence suggesting that a weekly injection of Wegovy can have a range of health benefits. This, researchers hope, will help Novo Nordisk’s case for insurers and governments to cover the costs of this expensive but effective drug.

The data was collected from the SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity) trial, which was designed to examine the drug’s impact on cardiovascular health. The trial – a multicenter, double-blind, randomized, placebo-controlled trial – studied patients with established cardiovascular disease who were also overweight or obese but did not have diabetes.

This resulted in 17,604 participants from 41 countries who were studied over four years. Around 72 percent of the participants were male, 84 percent were white, and the average age was around 62 years. Those who took part were given either semaglutide or a placebo for the trial’s duration.

In 2023, the researchers published the trial’s preliminary results, which showed that the drug could reduce participant’s risk of heart attack, stroke, and heart disease related deaths by 20 percent for just over three years.

In this latest analysis, those who took semaglutide saw their weight gradually drop by 10 percent, on average, over the first 65 weeks of the trial. Although it then plateaued, the initial loss remained for the 208 weeks of follow-ups. In comparison, those in the placebo group only lost 1.5 percent weight, which indicates an 8.7 percent treatment difference.

“Our long-term analysis of semaglutide establishes that clinically relevant weight loss can be sustained for up to four years in a geographically and racially diverse population of adults with overweight and obesity but not diabetes,” Professor Donna Ryan, a professor at Pennington Biomedical Research Centre in New Orleans who led the study, explained in a statement.

“This degree of weight loss in such a large and diverse population suggests that it may be possible to impact the public health burden of multiple obesity-related illnesses. While our trial focused on cardiovascular events, many other chronic diseases including several types of cancer, osteoarthritis, and anxiety and depression would benefit from effective weight management.”

There were no unexpected safety outcomes with semaglutide during the SELECT trial. The number of people who did experience severe adverse events was actually lower in the semaglutide group than in the placebo group and was mostly driven by differences in cardiovascular disorders.

However, semaglutide does not agree with everyone. Some people had to discontinue the trial as the escalation in the dose of the drug led to nausea and diarrhea.

In a second study, researchers examined the relationship between weight measures at baseline and changes in weight during the study with cardiovascular outcomes. This study found that patients in the trial experienced heart benefits from taking the drug, regardless of their weight when they started on semaglutide and regardless of how much weight they lost.

In essence, even patients with relatively mild levels of obesity or who only lose a modest amount of weight may experience improved cardiovascular outcomes.

“These findings have important clinical implications,” Professor John Deanfield from University College London added. “Around half of the patients that I see in my cardiovascular practice have levels of weight equivalent to those in the SELECT trial and are likely to derive benefit from taking Semaglutide on top of their usual level of guideline directed care.

“Our findings show that the magnitude of this treatment effect with semaglutide is independent of the amount of weight lost, suggesting that the drug has other actions which lower cardiovascular risk beyond reducing unhealthy body fat.”

These alternative mechanisms could include positive influences on blood pressure, blood sugar, or inflammation. They may also have a direct impact on the heart muscles and blood vessels, or maybe a combination of one or more of them.

Despite these significant results, it is important to stress that the findings from the SELECT trial should not be generalized to suggest that all adults who are overweight and have obesity will have the same outcomes. Even though the trial included a large and diverse population, it is not enough to rule out different results.

The first paper is published in Nature Medicine.