The weight loss drug Wegovy lowered heart attack risk in a large trial

PHILADELPHIA CREAM— At the recent American Heart Association meeting, a cavernous room full of doctors erupted in applause. Cardiologist A. Michael Lincoff of the Cleveland Clinic had just presented the spectacular – and sometimes enigmatic – results of a new clinical trial of semaglutide, a weight-loss drug.

The drug, sold under the brand Wegovy,reduce the risk of major cardiovascular problems in patientsby 20 percent, Lincoff reported on November 11. It also reduced the risk of death – from any cause – during the roughly 40 months that patients participated in the study on average.

Lincoff’s work attributes another role to semaglutide, which doctors currently use to treat diabetes and obesity. Previous work had already shown a cardiovascular benefit in people with type 2 diabetes. The new study, which targeted overweight or obese patients with cardiovascular disease, is the first to show that semaglutide can also help the heart of non-diabetic people.

That’s important because it increases the number of people who could benefit from the drug, says Tiffany Powell-Wiley, a cardiologist and epidemiologist at the National Heart, Lung and Blood Institute in Bethesda, Maryland. In the United States alone, more than 6 million people who are obese or overweight suffer from cardiovascular disease but not diabetes. Semaglutide could be a game-changer for these people, says Powell-Wiley, who was not part of the new trial. Still, she and others at the meeting acknowledged the study’s limitations — and those of the drug.

Although we want a quick solution to the increasing levels of obesity seen around the world, Powell-Wiley says: “It is important to understand that this is not a panacea. » We still don’t know how well semaglutide works in a diverse group of people, she says. And the drug doesn’t address the societal, environmental and social factors that lead to obesity – and its potential health consequences – in the first place.

Semaglutide reduced the risk of heart attack, stroke and death

Semaglutide is part of a family of drugs that are gaining popularity for treating obesity. On November 8, the United States Food and Drug Administrationapproved a new one: tirzepatide, a relative of semaglutide which goes by the brand name Zepbound.[See also: Semaglutide FAQ ]

Semaglutide, sold under the brand name Ozempic, hit the market for the treatment of diabetes in 2017. Since then, the drug’s many uses have continued to grow. In 2020, the FDA approved it to reduce cardiovascular risk in people with diabetes and heart disease. And in 2021, obesity treatment (with the higher dose of Wegovy) joined the list.

Lincoff’s semaglutide trial, called SELECT, included more than 17,000 people, half of whom received weekly semaglutide injections for about three years; the other half received a placebo. By the end of the trial, 8% of people in the placebo group had had a nonfatal stroke or heart attack or died from cardiovascular causes. This numberfell to 6.5 percent in the semaglutide groupLincoff reported at the meeting and online Nov. 11 in theNew England Journal of Medicine.

The difference between the two groups may seem small, but “it’s a huge result,” says Amit Khera, a cardiologist at UT Southwestern Medical Center in Dallas, who was not involved in the trial. The importance of finding a new treatment for patients with cardiovascular disease should not be underestimated, he says.

The disease is “the greatest source of mortality in the world,” Lincoff said at a Nov. 10 news conference, and there is no single treatment to eliminate it. Instead, doctors try to reduce this problem with various treatments that offer additional benefits.

For overweight or obese people with heart disease, Khera says, semaglutide is another tool in the cardiologist’s toolbox.

Questions remain about how the drug works – and for whom

The new results of the study become clearerEarlier news of the trial released by leaker Novo Nordisk in August (SN: 08/29/23). At the time, doctors wanted to know who this drug helped, how it worked, and what side effects it caused. The latest report offers answers to some questions but opens others.

Participants taking semaglutide were slightly more likely to drop out of the trial than those taking the placebo. This difference appears to be due to the drug’s gastrointestinal side effects, including nausea, diarrhea, and vomiting. The number of serious problems that occurred, such as cancer or infection, was slightly lower in the semaglutide group.

Although semaglutide offers clear cardiovascular benefits to patients, a puzzling aspect of the data has caught the attention of researchers. The drug’s protective effects became apparent early in the trial, well before participants had lost many pounds.

That’s a big deal because it suggests that semaglutide might directly improve heart health, perhaps in addition to the typical benefits that come with weight loss, says Caroline Apovian, an obesity medicine specialist at Harvard Medical School. and at Brigham and Women’s Hospital in Boston. She was not involved in the study but is part of Novo Nordisk’s scientific advisory board. Lincoff said his team is “working feverishly” to analyze the SELECT data to better understand the actions of semaglutide.

This data includes demographic and medical information on thousands of trial participants. But the trial has a “huge limitation,” says Powell-Wiley: 84% of study participants were white and 72% were men.

Expanding the diversity of people represented in clinical trials like this is crucial, she said. It was a point she raised during a panel discussion after Lincoff’s speech and which, like the trial results, drew widespread applause. In the United States, African Americans, Hispanics and Indigenous people are most affected by obesity, says Powell-Wiley, and the new trial doesn’t tell us much about how semaglutide works in these groups. .

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