The benefits of the drug semaglutide, sold under the brand names Ozempic and Wegovy, seem to go beyond controlling diabetes and helping people shed pounds. New research shows that the drug also has cardiovascular benefits and may lead to a better quality of life for people with heart problems who are also overweight.
In a trial of more than 500 patients with obesity and heart failure in 13 countries, those who got a weekly injection of semaglutide over the course of a year reduced symptoms such as fatigue, shortness of breath, and swelling. They also had notable improvements in their physical abilities and exercise function. The findings were published in late August in the New England Journal of Medicine.
Heart failure is a condition in which the organ struggles to pump enough blood to meet the body’s needs, because it is either too weak or not elastic enough. The patients in this study had a common type of heart failure in which the heart pumps normally but is too stiff to fill properly.
The prevalence of this medical condition has been rapidly rising, says Mikhail Kosiborod, a cardiologist at Saint Luke’s Mid America Heart Institute in Kansas City and lead investigator of the trial. “In addition to increasing the risk of death and hospitalization, it’s a real burden on patients in terms of debilitating symptoms,” he says. People get tired easily and often have trouble doing everyday activities, such as taking a shower, getting dressed, going to the supermarket, and walking.
Kosiborod says there’s growing evidence that obesity is not just coincidental in these patients, but may be the root cause of their heart failure. So researchers turned to semaglutide to see if the drug could alleviate the symptoms by targeting their weight. “What we observed was quite remarkable,” Kosiborod says.
On a 100-point scale commonly used to assess symptoms and quality of life for patients with heart failure, trial subjects taking semaglutide had a nearly 17-point improvement compared to a placebo group, which had an almost 9-point improvement. Patients taking semaglutide lost an average of 13.3 percent of their body weight, compared to a 2.6 percent reduction in the placebo group. They were also able to walk 20 meters (65 feet) farther in a six-minute test used to assess endurance and had fewer hospitalizations and emergency visits during the year-long study period.
Obesity may lead to heart failure in a few different ways. Too much weight gain can cause inflammation, including in the heart. That inflammation can make the heart stiffer and increase the risk of failure. Greater body weight also means more blood volume, which can increase the pressure inside the heart and cause congestion. High blood pressure can also cause the heart muscle to thicken, which can lead to the heart being too stiff to pump enough blood to the body.
Kosiborod says weight loss explains some of the benefits of semaglutide for patients with heart failure, but not all. He says it’s likely that semaglutide is working in other ways that researchers don’t yet fully understand.
The trial was sponsored by Novo Nordisk, which makes Ozempic and Wegovy. Semaglutide was originally developed by the company as a medication to treat type 2 diabetes. (It has been approved by the US Food and Drug Administration as Ozempic for diabetes and Wegovy for weight management, although Ozempic is also prescribed off-label for weight loss.)
People with type 2 diabetes don’t make enough insulin or are resistant to it. Semaglutide mimics the GLP-1 hormone, which is produced in the gut and regulates blood sugar by prompting the body to make insulin. This hormone also interacts with the brain to regulate appetite, and the drug version leads to weight loss by signaling a feeling of fullness so people eat less.
In addition to looking at how the drug may reduce heart failure in people with obesity, Novo Nordisk is researching whether it offers more general cardiovascular benefits. Last month, the company announced that weekly injections of semaglutide over a five-year period reduced the risk of stroke and heart attack by 20 percent in more than 17,000 people with obesity and a history of cardiovascular disease. The company hasn’t published detailed results from that trial yet, but it is expected to reveal them at a conference later this year.
“That is really exciting,” says Martha Gulati, director of preventive cardiology in the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles. Because being overweight or obese also increases the risk of stroke and heart attack, she expects patients who lose weight to have fewer of these events.
But Gulati says “that big of a reduction in cardiovascular events tells me there’s something else going on.” She says it’s possible that semaglutide is having an anti-inflammatory effect, for example. “I don’t think we entirely know how the drug works right now,” she says.
There’s also early evidence to show that Ozempic and Wegovy may dampen alcohol cravings. An independent study published in June by researchers in Sweden found that giving the drug to alcohol-dependent rats reduced their alcohol consumption by 50 percent.
Nathan Wong, director of the Heart Disease Prevention Program at the University of California at Irvine School of Medicine, says the heart failure results, combined with Novo’s recent announcement, are promising. “This expands the potential usefulness of this medication,” he says.
The latest findings build on trial results published in 2021, which found that for overweight or obese people, the drug reduced body weight by an average of 14.9 percent and led to reductions in certain cardiovascular risk factors, such as blood pressure and the level of lipids, or fatty compounds in the blood.
Based on that 2021 paper, Wong and his colleagues used statistical modeling to estimate how many Americans may benefit from semaglutide. His study, published in August, concluded that if all 93 million US adults who are overweight and obese were prescribed the drug, over it could result in 43 million fewer people with obesity, and over 10 years, prevent up to 1.5 million heart attacks, strokes, and other adverse cardiovascular events.
Currently, statins are the most widely used medicine to reduce the risk of heart attack and stroke. They work by lowering LDL, or “bad,” cholesterol and have been shown to slash cardiovascular risks. Semaglutide may offer additional benefits for people already taking statins.
Broader heart benefits could mean more people will want to take Ozempic and Wegovy. But for that to happen, Wong says, the drugs will need to be more accessible. Without insurance, Ozempic’s list price is $935 and Wegovy’s is $1,350 for a monthly prescription in the US. (A version for cardiovascular disease could come with a different price tag and brand name.) Even with insurance, some people may not be able to afford copays, and supplies of the drug are currently limited because of high demand.
Novo Nordisk plans to seek regulatory approval in the US and Europe for more uses of semaglutide. Once a drug is already on the market, the approval process for additional indications is usually speedier, since the drug has already been shown to be safe. If it’s granted, this blockbuster drug could become its own sequel.
