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.