Topline data show semaglutide cuts CV risk by 20%: SELECT
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Key takeaways:
- Semaglutide 2.4 mg was shown to reduce risk for major adverse CV events by 20% in people with obesity and CVD.
- The data are the first to show a reduction in hard CV outcomes for an obesity treatment.
Compared with placebo, injectable semaglutide 2.4 mg reduced risk for major adverse CV events by 20% for people with overweight or obesity and established CVD, according to topline data from the SELECT study.
The data are the first to demonstrate a reduction in hard CV outcomes for a drug approved for chronic weight management in a large, randomized controlled trial.
For SELECT, researchers analyzed data from 17,604 adults aged 45 years or older with overweight or obesity and established CVD but without diabetes, randomly assigned once-weekly semaglutide 2.4 mg (Wegovy, Novo Nordisk) or placebo, with follow-up for 5 years, according to a press release from Novo Nordisk. The primary endpoint was a composite outcome of the first occurrence of major adverse CV events, defined as CV death, nonfatal MI or nonfatal stroke.
During follow-up, researchers observed 1,270 major adverse CV events.
The trial achieved its primary objective by demonstrating a statistically significant and superior reduction in major adverse CV events of 20% for participants assigned semaglutide 2.4 mg compared with placebo, and all three components of the primary endpoint contributed to the superior major adverse CV event reduction, according to a press release from Novo Nordisk.
“These results, a 20% reduction, rivals the statin trials from past decades,” Howard Weintraub, MD, clinical director of the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, professor in the Leon H. Charney Division of Cardiology, NYU Grossman School of Medicine, and an investigator for the SELECT study, told Healio. “This is occurring on top of very good baseline therapy, with statins and BP medications, in people without diabetes. About three-quarters of participants had an MI and about one-fifth of participants had a stroke as entry criteria. This is a very important trial that will change the way we look at a very potent risk factor.”
During the trial, the drug was well tolerated with no serious safety events observed, in line with previous semaglutide 2.4 mg trials, the company stated in the release.
"People living with obesity have an increased risk of CVD but to date, there are no approved weight management medications proven to deliver effective weight management while also reducing the risk of heart attack, stroke or cardiovascular death,” Martin Holst Lange, executive vice president for development at Novo Nordisk, said in the release. “Therefore, we are very excited about the results from SELECT showing that semaglutide 2.4 mg reduces the risk of CV events. “SELECT is a landmark trial and has demonstrated that semaglutide 2.4 mg has the potential to change how obesity is regarded and treated.”
In the release, Novo Nordisk stated it expects to file for regulatory approvals of a label indication expansion for semaglutide 2.4 mg in the U.S. and the European Union in 2023.
Weintraub said these data underscore the importance of treating obesity in people with CVD.
“This underlines that a GLP-1 receptor agonist has weight loss benefits as well as other cardiometabolic benefits that have been known to reduce CV events,” Weintraub said during an interview. “This drug is going to be a friend with benefits and a good utility player.”
The full results from SELECT will be presented at a scientific conference later in 2023, the company stated in the release.
Perspective
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Ian J. Neeland, MD, FAHA, FACC
This is the first randomized controlled trial data we have that shows treating obesity in people without diabetes can reduce CV risk, something we tried to see in the LOOK AHEAD trial using intensive lifestyle intervention. Semaglutide 2.4 mg, beyond robust weight reduction and improvements in surrogate markers of CVD, such as lipids and glucose, is now associated with benefits for hard CV outcomes — CV death, nonfatal MI and nonfatal stroke.
The topline results show that the composite outcome was driven by all three components. This is interesting, considering that for previous SGLT2 inhibitor trials, there was no stroke benefit. In the LEADER trial with liraglutide (Victoza, Novo Nordisk), there was a modest stroke benefit. That is a potentially differentiating factor for cerebrovascular disease.
What this means, to me, is when you have a patient struggling with overweight or obesity and established CVD, we now have a very strong indication, from a CV standpoint, to treat someone with GLP-1 receptor agonist like semaglutide. This will, hopefully, take a lot of the stigma out of obesity treatment for the CV community. We treat risk factors, and overweight and obesity are strong risk factors for CVD. Now, we have clear data to show treatment with a pharmacologic agent can reduce CV risk for secondary prevention.
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Carl J. Lavie Jr., MD, FACC, FACP, FCCP
This is very exciting news and I anxiously await the presentation and paper that will likely be in The Lancet or The New England Journal of Medicine. Demonstrating clinical event reduction in patients without type 2 diabetes is a very big deal, and will likely put this very safe and effective medication into the forefront.
Clinicians will start using semaglutide 2.4 mg not just for weight loss but also for clinical event reduction, even for patients without type 2 diabetes with CVD, similar to the way SGLT2 inhibitors are used for the prevention of HF in type 2 diabetes and for treatment of HF in people without diabetes. Very importantly, the price to patients should eventually fall, making the agent more affordable.
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