The cardiovascular benefits of Novo Nordisk’s blockbuster weight loss drug Wegovy are not dependent on the amount of weight patients lost, according to a new analysis.
The findings from the analysis of Novo’s SELECT trial suggest that the heart protection offered by Wegovy goes beyond the cardiovascular improvements that come from weight loss. However, researchers said that they can’t yet pinpoint what is driving the treatment’s beneficial effects on heart health.
A. Michael LincoffNovo markets semaglutide in both type 2 diabetes as Ozempic and for weight loss as Wegovy.
“We can’t couple the amount of cardiovascular risk reduction with the amount of weight loss,” said Cleveland Clinic cardiologist A. Michael Lincoff, who led the study. “Patients who lost a lot of weight or patients who lost a small amount of weight seem to experience the same amount of cardiovascular benefit.”
In the latest analysis of the SELECT trial, which was presented this week at the European Congress on Obesity in Venice, 17,000 patients received either Wegovy or placebo. They were then divided into two groups: those who lost at least 5% of their weight, and those who lost less than 5% or gained weight.
Hertzel GersteinThe results showed that people taking Wegovy who lost more weight and those who lost little to no weight saw similar reductions in risk of stroke, heart attack or cardiovascular death.
Hertzel Gerstein, deputy director of the Population Health Research Institute at McMaster University and Hamilton Health Sciences in Hamilton, Canada, told Endpoints News that he is “not surprised at all” by the results.
Beyond weight loss
Researchers don’t know what exactly leads to the cardiovascular benefit in patients taking Wegovy. There could be a myriad of reasons.
“The drug definitely has effects on the brain. Also, there’s a lot of other possible effects that may explain any cardiovascular benefit,” Gerstein said. “But there’s also the fact that the drug itself is a cardiovascular drug and so maybe it’s that binding to the GLP-1 receptors throughout the body, and they’re distributed throughout the vascular system, throughout the brain, throughout the heart and everywhere else. Perhaps that accounts for the cardiovascular benefits of the drug.”
Caroline ApovianOne hypothesis that obesity experts suggested is that Wegovy’s ability to lessen inflammation fuels cardiovascular benefits. “Many people think that part of the reduction in cardiovascular risk is from a reduction in inflammation,” said Caroline Apovian, co-director of the Center for Weight Management and Wellness at Brigham and Women’s Hospital in Boston. “We’d have to prove that.”
Apovian pointed out that reducing inflammation could be beneficial for lowering the risk of Alzheimer’s disease progression. Novo Nordisk is already studying semaglutide in a Phase 3 trial for early Alzheimer’s.
The SELECT trial last year showed that Wegovy reduced the risk of stroke, heart attack or cardiovascular death by 20% in patients who are obese or overweight and who do not have diabetes. Research has long shown that patients with diabetes see a benefit to their cardiovascular health when they lose weight.
The FDA in March approved Wegovy as a CV treatment for that patient group — an important expansion for patients covered by Medicare, which is barred from reimbursing medicines used solely for weight loss.
In the results shared Tuesday, the data show that weight loss continued over 65 weeks (15 months) and was sustained for up to four years. At 208 weeks (nearly four years), semaglutide was associated with a mean reduction in weight of 10.2%.
Are GLP-1s the new heart drug?
The study’s findings raise questions about Wegovy’s broader promise: Could the drug supply heart benefits to people who don’t lose any weight?
Phil Scherer“We have to be careful in terms of jumping to the conclusion that GLP-1 receptor agonism has cardiometabolic benefits without any weight loss at all, because again the vast majority of the patients lose a little bit of weight,” said Phil Scherer, director of the Touchstone Diabetes Center at UT Southwestern Medical Center. “We know from decades worth of analysis that this is beneficial.”
Eli Lilly is awaiting the results of its large cardiovascular outcomes trial for tirzepatide, which it markets as Mounjaro for diabetes and Zepbound for weight management. Lilly’s outcomes study in type 2 diabetes patients is expected to read out next year, while its study in adults with obesity is expected to read out in 2027, according to the federal clinical trials database.
Lincoff, who led the Novo study, said the study results mean that all GLP-1 therapies can’t be assumed to have the same magnitude of cardiovascular benefit. “What it means is that we’re going to need the actual trials to prove the cardiovascular benefit,” Lincoff said. “You can’t prove it through a surrogate of weight loss or glycemic control.”
However, researchers are still optimistic that heart protection will be seen in all incretin-based drugs. “The anticipation is very much that this will be a class effect,” Scherer said.
Editor’s note: This story was updated to correct the timing of Eli Lilly’s trial readouts.