Diseases involving the heart and blood vessels are the leading cause of death globally and in the US. So anything that helps reduce deaths due to cardiovascular disease is a cause for celebration, whether its effect is modest or major.
But rarely does an intervention come along with as big a potential impact on mortality as the latest one: In a news release yesterday, the maker of the diabetes and weight loss drug semaglutide (branded as Wegovy and Ozempic) said the drug reduced the risk of serious cardiovascular events, including death, heart attack, and stroke, by 20 percent.
“People are very excited,” said James Januzzi, a cardiologist and researcher at Massachusetts General Hospital in Boston, who was not involved in the study. “Although we have been able to slow the tide of heart disease in the last 20 years, a lot of those gains have started to be lost because of the rise of obesity and diabetes.”
It was reasonable for researchers to expect that simply by helping people lose weight, semaglutide would also offer a protective effect against heart disease.
But they might not have guessed at how big that effect would be — and it’s huge.
“Twenty percent — that’s considered big” in the heart disease world, said Joseph C. Wu, director of the Stanford Cardiovascular Institute and president of the American Heart Association.
There’s a lot of deserved excitement around this press release. Still, it was just a press release, not a peer-reviewed publication.
A full publication of the study, called SELECT, will follow in a peer-reviewed journal in time. The complete report might reveal a few wrinkles, and will hopefully help answer a variety of questions about how the drug works, how it should be used, and whether it can be distributed equitably.
But in the meantime, many experts share Wu’s hope that as an additional tool in the toolbox, semaglutide could be an incredibly powerful tool for reducing deaths due to heart disease.
Early results suggest semaglutide could offer lifesaving benefits to a much bigger group of patients than initially thought
The news release from semaglutide maker Novo Nordisk gave a rough sketch of results from the SELECT clinical trial, which followed 18,000 adults taking the medication for up to five years.
The press release lacks many details of a full, peer-reviewed publication, including critical details clinicians use to make changes in how and to whom they prescribe the drug.
But in the meantime, what’s most exciting about the trial is who it studied: adults who were overweight or obese (with a body mass index, or BMI, of 27 or higher), age 45 or over, and with “established cardiovascular disease” (which includes people who’ve had chest pain due to blockage of a blood vessel in the heart, or have other evidence of blood vessel blockages).
This different study population represents a lot of people in the real world — many of us know relatively young, healthy whose health could be affected by the results of this trial.
Notably, the patients included in the trial did not have diabetes. The drug has already been shown to reduce cardiovascular risk in that group; the latest study was designed to look at people who were overweight or obese, and who despite not having diabetes, still had higher-than-average risk of heart attack, stroke, or another serious cardiovascular event.
What the trial showed was remarkable: Compared with a placebo, semaglutide reduced the risk of serious cardiovascular events by 20 percent in the study group.
Other drugs have achieved similarly dramatic results in lowering cardiovascular risk —cholesterol-lowering statins, for example, also achieve big risk reductions, even in low-risk adults. But presumably, the adults in the SELECT trial were already receiving those other drugs, said Wu, and semaglutide provided an additional above-and-beyond benefit. “The 20 percent on top of the medications that patients are already taking, that’s pretty impressive,” he said.
It’s not clear yet how semaglutide works to reduce heart disease risk.
The news release doesn’t answer all the important questions about this finding. It’s not entirely clear how semaglutide lowers cardiovascular risk.
It could be that it’s purely the weight loss induced by the drug that helps people.
“Obesity in and of itself is accompanied by a number of metabolic abnormalities that predispose one to cardiovascular events,” Januzzi said. That means that no matter how it happens — semaglutide-induced or not — weight loss itself reduces heart disease risk.
But there’s a strong possibility that semaglutide offers protective benefits above and beyond the weight loss associated with taking it.
“My hunch is that besides the weight loss,” said Wu, “this medication probably has some other beneficial effects, such as anti-inflammation and anti-plaque.” (Plaques are the fatty deposits on blood vessel walls that dramatically raise the risk of heart attack and stroke.) He suspects the drug’s effects are a result of all of these positive effects added together.
There are still many unanswered questions about semaglutide — and a published study will only answer some of them
It’s still unclear how semaglutide will figure into medication regimens for people in the future — that is, how and whether it will replace other drugs, at what dosages it will be prescribed, and for whom.
One important open question is whether the heart disease risk reduction is proportional to weight loss, said Wu. If it’s not, that suggests the drugs effects come from more than just its ability to reduce people’s weight — and that even a small dose of the drug could have a beneficial effect.
Wu’s also curious about the drug’s effects on blood pressure, blood sugar, and cholesterol — all of which independently increase cardiovascular risk. Understanding these effects, and whether semaglutide improves on other drugs that study patients were taking to address these issues, will be important for eventually determining how to streamline patients’ medication regimens. (For example, if it turns out semaglutide duplicates all the effects of a statin, patients might not need both.)
And he has questions about whether everyone is likely to get the same protective benefits from the drug. “Is there a particular age group that benefits more than another? Is there a particular ethnicity group that benefits more than another?” said Wu.
He hopes more details on the SELECT study’s results will provide answers to these questions, although he also has some questions that would require additional studies to answer. He’s especially interested to know if the drug also has a protective effect for people with BMIs below 27. If it does, that would expand the range of people eligible to benefit from the drug even further than the SELECT study appears to do.
Januzzi is also curious if patients who can only tolerate lower doses of semaglutide due to side effects — such as nausea — will also get benefits from it. “Nothing in medicine is one size fits all,” he said, “so understanding if reducing the dose is associated with similar benefits will be important.”
The biggest question of all — how much will people pay for these reported benefits?
Regardless of the answers to these medical questions, there will be some obstacles to overcome before semaglutide is available to everyone who could benefit from it. Access to the drug has already been limited by low insurance coverage and shortages stemming from manufacturing issues and supply chain problems.
If the drug does become the standard of care for people at risk for heart disease, there will be a lot of interest in increasing its supply. “In a free market, I’m sure there’ll be other drug companies that come up with similar types of tools,” said Wu. He hopes competition will eventually drive down the price of semaglutide and similar drugs.
Drug pricing would play an important role in determining whether insurance companies cover the drug — a major concern to Januzzi. Currently, patients often pay a lot of money out of pocket to get the drug, and its steady availability is far from a sure thing. “So there are open questions that relate less to the clinical trial and more to everyday clinical practice,” he said.
But even without total clarity on the way forward, the news on semaglutide’s potential beyond treating diabetes and obesity is pretty earth-shaking, Januzzi said. “There are things that happen once every 10 years or so,” he said — and this is one of them.