PHILADELPHIA – Wegovy, Novo Nordisk’s anti-obesity drug, markedly reduced the risk of heart attacks in a landmark cardiovascular trial that claims the treatment offers health benefits beyond weight loss.
In August, the company had announced that in this trial, called Select, Wegovy reduced the overall rate of major heart problems (heart attacks, strokes or deaths related to cardiovascular diseases) by 20%. That finding, which was the main result the trial set out to study, was stronger than many expected and led to Novo’s stock rising.
But details of the study, including the risk reductions for each specific heart complication, were not released until Saturday, when they were presented here (to a standing-room-only crowd) as the first major session of the conference. American Heart Association.
The overall 20% reduction in the risk of heart problems translated into 15 complications avoided per 1,000 patients treated.
Wegovy specifically reduced the rate of heart attacks by 28% among patients who were already taking statins and other medications to prevent heart problems, according to the results, published simultaneously in the New England Journal of Medicine. The drug also reduced the rate of deaths related to cardiovascular diseases by 15% and strokes by 7%.
Additionally, people in Wegovy experienced a 19% lower rate of death from any cause.
Partly because of the way the trial was designed, the primary outcome looking at overall cardiovascular risk was the only outcome that was considered statistically significant. Still, doctors praised the full findings, especially the reductions in rates of heart attacks and deaths from all causes.
The study had “really impressive overall results,” said Nicholas Marston, a cardiologist at Brigham and Women’s Hospital who was not involved in the study, noting that the reduction in overall cardiovascular risk emerged early on and continued to increase over the course of the trial. .
Wegovy, along with its sister diabetes drug, Ozempic, are part of a growing class of GLP-1-based medications, whose popularity has skyrocketed for causing substantial weight loss. But insurers have been reluctant to pay for the drugs, considering them cosmetic rather than medical treatments. Select is the first trial to demonstrate that an anti-obesity drug improves cardiovascular outcomes, representing a key milestone not only for Novo, but also for the field of cardiology.
“This is the first weight management therapy that we have shown in a rigorous trial to reduce the excess risk of cardiovascular events associated with overweight and obesity,” A. Michael Lincoff, principal investigator of the trial and interventional cardiologist at the Cleveland Clinic . , he said in an interview. “This now establishes that overweight and obesity is a new pathway, another modifiable risk factor, that we can treat in patients with cardiovascular disease.”
However, there are still many questions about how the drug produces cardiovascular benefits, and researchers are investigating whether weight loss alone contributed to the result or whether there are additional factors.
Select’s results come as Novo faces increased competition from Eli Lilly, which just received approval to sell its diabetes drug Mounjaro as an obesity treatment under the name Zepbound. Lilly’s drug has shown potential for greater weight loss, which likely makes it more attractive to many patients, but Wegovy now has tangible data supporting its cardiovascular benefits.
That could help convince payers to increase access. Insurers have objected to the price of the drug, which costs more than $16,000 a year and must be taken indefinitely. Select’s data could bolster Novo’s arguments that Wegovy will prevent heart problems and reduce long-term costs.
The results may even help you obtain Medicare coverage, which is prohibited by law from covering weight-loss medications. Doug Langa, head of the company’s North American operations, said on an earnings call last week that the cardiac data may lead Novo to try to request an exception for Wegovy.
Longest trial yet for Wegovy
Select enrolled more than 17,600 people with obesity and existing heart disease and without diabetes.
It lasted five years, making it the longest trial conducted for Wegovy and allowing it to provide a window into the drug’s long-term efficacy and safety. Patients taking Wegovy lost on average about 10% of their weight and maintained the weight loss throughout the trial. That’s less than the weight loss shown in a previous large Wegovy trial, which was about 15 percent, but Lincoff noted that the earlier study specifically studied weight loss and included lifestyle interventions.
About 17% of people taking Wegovy stopped treatment due to adverse events, more than the 8% who stopped in the placebo group. The most common reason people stopped taking the drug was gastrointestinal problems, similar to Wegovy’s previous trials.
Concerns have recently arisen that GLP-1-based medications may increase the risk of suicidal thoughts. However, the trial found that 0.7% of patients taking Wegovy experienced psychiatric disorders, about the same as 0.6% of patients taking placebo.
One limitation of the trial is that men made up nearly three-quarters of the participants, said Martha Gulati, director of preventive cardiology at Cedars-Sinai Medical Center, who was not involved in the study. While she also found her results impressive, she said it was disappointing that more women were not included, especially since there has been a historical problem of women being underrepresented in cardiac trials.
Lincoff said the researchers attempted to enroll a diverse group of participants, “but we ultimately ended up with a group of patients that does not duplicate a globally representative patient population.” However, she doesn’t think that influenced the trial results, “since the subgroups were of significant size in this large trial and the women and men [had] similar treatment effects.
The trial occurred during the Covid pandemic, which presents a challenge. Researchers are investigating whether some deaths may have been misclassified as not related to cardiovascular disease, as researchers may have had less information about patients who did not seek care during the pandemic, Lincoff said in presenting the findings.
What drove the cardiovascular benefit?
A key question for researchers and companies developing anti-obesity drugs is to what extent the cardiovascular benefit seen in this trial was driven by weight loss or by other pharmacological mechanisms. If weight loss were the main factor, that suggests that drugs that lead to greater weight loss, like Lilly’s Zepbound, could also have greater cardiovascular benefit. But if factors other than weight loss were involved in this trial, then it would be more difficult to infer how much cardiac benefit other drugs might provide.
Michael Mason, who heads Lilly’s diabetes and obesity unit, raised this point on an earnings call last week, saying that “probably the key question I’m looking at [for the Select trial] “It’s how much of the effect was driven by the effect of the drug versus the weight loss.” Lilly is conducting a similar trial looking at the long-term health outcomes of Zepbound, but it is not expected to be completed until 2027.
Lincoff noted that in Select, since the reduction in the risk of cardiovascular problems occurred early, before large weight changes, “that implies that there is [an] “The effect that occurs is independent of the amount of weight lost,” he said.
Additionally, the fact that people in the trial did not lose as much weight as seen in previous studies and still experienced cardiovascular benefits further supports the idea that weight loss is not the only factor at play, said Randy Seeley, director of Michigan Nutrition Obesity. Research Center that did not participate in the study.
Some data suggest that GLP-1-based treatments have anti-inflammatory effects, which could be beneficial for the heart. There are also GLP-1 hormone receptors located on heart cells, and the drug’s direct effect on those receptors may also play a role.
This study did not look at the relationship between the magnitude of participants’ weight loss and their cardiovascular risk reduction, but researchers are planning follow-up analyses, Lincoff said.
Ultimately, he said, “I think it’s a combination of multiple different effects: the magnitude of weight loss, the process and mechanism by which you lose weight, and other effects on blood sugar, inflammation, blood pressure and perhaps direct effects of the drug on the heart and blood vessels themselves.”
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