A powerful anti-obesity drug offers strong protection against serious heart disease, surprising researchers in clinical trial results who say the discovery could change how the drug and other new generations of obesity treatments are used and who gets to take them.
Full data from clinical trials of Wegovy (the brand name for the drug semaglutide) have not yet been released. But results published by manufacturer Novo Nordisk, based in Bagsvaer, Denmark, showed that taking Wegovy weekly reduced the risk of serious cardiovascular events by 20% in overweight or obese adults with heart disease. These are the first results to suggest that semaglutide may prevent serious cardiovascular events in people without type 2 diabetes.
If confirmed, the researchers say the findings could change the practice of preventive cardiology. They also suggest that a new generation of anti-obesity drugs could do more than just reduce weight; they could significantly improve health. “This is probably the most important study in this field in the last decade,” says Michael Blaha, director of clinical research at the Johns Hopkins Ciccarone Center for the Prevention of Cardiovascular Disease in Baltimore, Maryland. “This study really gets at a cardiometabolic risk that’s been difficult to treat.”
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“It’s hard to think of anything else [drugs]”No other drugs other than statins have shown such a significant effect,” says Martha Gulati, director of preventive cardiology at Cedars-Sinai Medical Center in Los Angeles, California.
When will more details be announced?
The full results of the trial are expected to be presented at a conference later this year. What we know so far is that the study, called SELECT, involved 17,604 people who already had cardiovascular disease but had no history of diabetes. Participants received either Wegovy or a placebo injection and were followed for up to five years. Those who received the drug had a lower risk of heart attack, stroke, and death from cardiovascular disease than those who received a placebo.
What drives risk reduction?
Semaglutide, sold under the names Wegovy for the obesity treatment and Ozempic for the diabetes treatment, works by mimicking a hormone called glucagon-like peptide 1 (GLP-1), which is involved in appetite regulation.
The researchers hoped that Wegobee would prevent heart disease. Obesity itself is an important risk factor for cardiovascular disease, and weight loss can lead to improvements in other risk factors, such as blood pressure and cholesterol levels. But changes in other factors can contribute to risk reduction. For example, there is evidence that drugs that mimic GLP-1 can improve fatty acid metabolism and reduce inflammation, Gulati says. “That’s what’s so fascinating about these drugs: they act on the brain, pancreas, cardiovascular system and gastrointestinal tract. It’s not just about losing weight.”
More data could help explain whether this protective effect is primarily associated with weight loss or is caused by other changes promoted by the drug.
Could the new obesity drugs prevent other diseases too?
Because obesity is associated with conditions such as high blood pressure, sleep apnea, and nonalcoholic fatty liver disease, “losing weight is likely to improve these comorbidities as well,” says Joseph Wu, M.D., president of the American Heart Association and a cardiologist at the Stanford University School of Medicine in California.
Blaha noted that the SELECT trial looked at a narrow range of serious cardiovascular events, which may have underestimated semaglutide’s benefits on cardiovascular health, as well as its potential to enhance athletic function, mood and other characteristics that tend to improve in people who experience weight loss.
Will the results change the way doctors prescribe medications?
A drug like Wegoby would likely be accepted by a broader range of health care providers, not just obesity specialists, says Beverly Chang, an endocrinologist at Weill Cornell Medical College in New York City. The study’s results support Wegoby as a cardiovascular drug as well as a weight-loss drug, she says.
Wu agrees: “We will likely see an increase in prescriptions for the drug for overweight patients with cardiovascular risk factors,” he says.
Reframing Wegovi as a treatment for cardiovascular disease rather than an obesity drug may also increase its acceptance as a long-term treatment. “People will take Wegovi more seriously as a treatment for heart disease,” Chan predicts.
Novo Nordisk plans to apply for approval of more conditions that could be treated with Wegovy in both the United States and Europe by the end of the year. Experts say the full trial results should provide enough evidence for the U.S. Food and Drug Administration to approve the drug for cardiovascular disease risk reduction. “I think the label changes will lead to more prescriptions for this drug,” Blaha says.
Cardiologists hope the SELECT trial results will help make the drug more widely available. Some U.S. insurers only cover the cost of the drug for people with diabetes. Doctors are eager to use the new GLP-1 mimetics, but “just giving patients hope is a good thing,” said Dr. [for them] “Insurance companies may turn them down,” Gulati said, but expanding coverage “would be a game changer in the clinical practice of preventive cardiology.”
This article is reprinted with permission. First Edition August 10, 2023.
