- Semaglutide, the compound on which weight-loss drugs Ozempic and Wegovy are based, significantly reduced the number of cardiac events in people without diabetes in a large new, randomized, controlled trial.
- Participants in the study all had pre-existing cardiovascular disease: a previous heart attack, stroke or symptomatic peripheral arterial disease and a BMI over 27.
- While the weight loss associated with semaglutide is likely one factor in the reduction of cardiac events, the study’s authors saw the number of events go down even before maximum weight loss occurred.
Semaglutide is the chemical name for the blood-sugar management drugs Ozempic, Wegovy, and Rybelsus, developed for people with diabetes. Ozempic and Wegovy are also approved as weight-loss medications in the U.S.
For people with overweight or obesity and pre-existing cardiovascular disease (CVD), taking semaglutide for three years resulted in 20% fewer heart attacks, strokes, and deaths, compared to those taking a placebo, according to the new study.
The randomized, controlled study recruited over 17,000 people with overweight or obesity and preexisting cardiovascular disease. None had type 1 or type 2 diabetes. In the end, 15,425 people completed the trial.
Participants in the study lost an average of 9.4% of their body weight on semaglutide.
Weight loss from semaglutide persists as long as one remains on the medication. Typically, it is taken for the remainder of one’s life.
While such a loss of weight may reduce risk factors for cardiovascular disease, the trial suggests that something more is going on.
The study was published in The New England Journal of Medicine.
Dr. A. Michael Lincoff explained that semaglutide is a GLP-1 agonist, and “It’s a hormone that’s derived from the gut.”
“GLP-1 agonists are released into the [gastrointestinal] system, and act by reducing appetite and hunger cravings by traveling to the hunger centers of the brain,” said Dr. Jayne Morgan, a cardiologist and clinical director of the Covid Task Force at the Piedmont Healthcare Corporation in Atlanta, GA, who was not involved in the study.
By stimulating receptors in the pancreas, semaglutide can stimulate the production of insulin, suppress glucagon, and slow gastric emptying. All of these actions have the effect of reducing appetite, and food intake.
The authors of the study suspect that it is not just weight loss that improved participants’ heart health.
“The maximum weight loss didn’t occur until 65 weeks after starting the drug, but we saw differences in the [number of cardiovascular] event rates very early on, within a few months of starting the drug,” said Dr. Lincoff.
Dr. Lincoff explained that GLP-1 agonists “stimulate the same receptors which are present in a lot of different parts of the body. They’re present in the gut, they’re present in the brain, and the heart and blood vessels, and the pancreas.”
Cardiologist Dr. Nicole Weinberg, who was also not involved in the study, suggested that semaglutide’s benefits for people with CVD may have to do with a reduction in blood sugars that produce inflammation throughout the body.
“The more chronic inflammation that you have in your system, the more at risk you are for a variety of different conditions,” said Dr. Weinberg.
“One of the biggest things that we worry about in cardiology is depositing, plaquing, or cholesterol or inflammation within the system. And a lot of that can come from this inflammation that you get with your blood sugars,” continued Dr. Weinberg.
In addition, jumps in blood sugar may not be restricted to people with diabetes.
“We’re starting to understand that people have spikes in their blood sugars, and even just spikes in their blood sugars are dangerous to people’s cardiovascular health,” added Dr. Weinberg.
Dr. Weinberg said she will advocate for semaglutide for certain patients:
“Perhaps their cholesterol and blood pressure are well-managed, but we’re still seeing that there are continued levels of atherosclerosis that are depositing despite what one would consider to be traditional medical therapy.”
Obesity’s links to health issues are often attributed to high blood pressure, diabetes, and other factors. However, Dr. Lincoff said obesity “carries an excess risk of heart disease, and that risk is not completely explained by or controlled by risks associated with high body weight.”
“Independently, obesity is associated with increased risk,” said Dr. Lincoff, and noted that semaglutide is the first therapy that can decrease that risk directly.
“We are in the same space now with high blood pressure, diabetes, smoking, and cholesterol as modifiable risk factors. [Obesity] stands next to those as another modifiable risk factor for controlling heart disease,” he said.
One real-world issue with semaglutide is its cost and availability.
Dr. Morgan cited the price for the drug as $1,300 per month, a particular problem if “this is a lifetime maintenance therapy for obesity, diabetes, and heart disease prevention and mitigation, at a cost of nearly $16,000 annually for this single medicine.”
Dr. Weinberg mentioned the limited nature of U.S. insurance coverage for semaglutide.
“It’s still not accessible to everybody. I think that with more studies and more data, it’ll become easier and easier for people to get access to this drug,” she said.
“But I don’t know that this is going to change things. I don’t think it’s going to [move] the needle significantly for patients, just because I think a lot of the resistance that we get is with insurance companies, as well as the availability of the drug,” she added.
Dr. Morgan would have liked to see a more representative sample of people included in the trials.
“Women were only included at 28% of the trial enrollees, yet comprise more than 51% of the world’s population. Further, menopausal women, with the greatest risk of heart disease, were not even identified in this trial,” she said.
“Black [people] fared even worse, only comprising just under 4% of trial participants,” she said, noting that they amount to almost 18% of the global population. Of the study participants, 85% were white, even though they account for just 9% of the world’s people.
While more research is called for and accessibility issues addressed, Dr. Morgan said “This is a potential game-changer for diabetes management, obesity management, and cardiovascular Health, especially as we age.”
“Heart disease is the [number] 1 cause of death in the U.S. Even at the height of COVID, heart disease was not dethroned,” she pointed out.
“With our growing obesity and diabetes epidemics in younger and younger demographics, the cardiac endpoints are critical pieces of information that continue to boost these compounds into prime time and beyond,” she noted.
