A new analysis of a major clinical trial affirmed that Wegovy, the popular obesity drug, lowers the risk of major heart issues like heart attacks and strokes in some adults, but showed that weight loss could not fully explain the cardiovascular benefits.
How else, exactly, the drug protects the heart remains a mystery.
Obesity is intricately linked with poor heart health, and losing excess weight can blunt the risk of cardiovascular concerns. But the analysis, published on Wednesday in The Lancet, found that a shrinking waist size — a measure of shedding belly fat — was responsible for only around a third of the observed cardiovascular benefits in people who took Wegovy. In their first 20 weeks of taking the drug, patients experienced cardiovascular benefits no matter how much weight they lost.
“As it stands now, we do not know how to account for that other roughly two thirds of the benefit,” said Dr. Michael Lincoff, a professor emeritus of medicine in the department of cardiovascular medicine at the Cleveland Clinic and an author of the paper.
The analysis parsed data from the largest and longest trial on semaglutide, the substance in Wegovy and its sister drug Ozempic. The study followed over 17,000 adults who were overweight or obese and had heart disease. (Novo Nordisk, the company that makes Wegovy and Ozempic, funded the research.) The drug appeared to lower the risk of heart attack, stroke or death from cardiovascular issues by 20 percent. Last year, that research led the Food and Drug Administration to approve Wegovy to lower the risk of those cardiovascular issues for some patients.
The new paper adds to the mounting evidence that Wegovy and similar medications have much broader uses than weight loss alone.
Over the last few years, research has shown that these kinds of drugs can treat severe liver disease, sleep apnea, kidney disease and other ailments. On Friday, the F.D.A. greenlit Rybelsus — a diabetes pill that also contains semaglutide — to cut the risk of cardiovascular issues like heart attacks and strokes in some adults with Type 2 diabetes.
“We are thinking they are no longer weight loss-drugs, but they are disease-modifying therapies for risk reduction,” said Dr. Yuan Lu, an assistant professor of cardiovascular medicine at the Yale School of Medicine who was not involved in the study. “I think this is a much bigger picture,” she added.
A leading theory for why these drugs have such broad benefits is that they may lower inflammation throughout the body. Scientists are trying to untangle how else the medications may help the heart: It may be because they help improve blood sugar and blood pressure levels. The drugs could also lower cholesterol or potentially reduce levels of plaque in the walls of blood vessels; together, these effects might help the heart.
“There’s all these other unexplained factors,” said Dr. Melanie Jay, the director of the N.Y.U. Langone Comprehensive Program on Obesity. “Really, you don’t know,” she added.
But even with these unknowns, the new findings suggest that people who do not meet the medical definition for obesity but are overweight and have already established cardiovascular conditions could benefit from a drug like Wegovy, said Dr. Clyde Yancy, the chief of the division of cardiology at Northwestern Medicine.
“We may have to re-examine how we dispense these drugs,” Dr. Yancy said.
The findings build upon previous research suggesting that the cardiovascular benefits of Wegovy begin before meaningful weight loss occurs, said Dr. Nils Krüger, a researcher at Harvard Medical School. Dr. Krüger published a paper over the summer that showed high-risk patients with heart failure were at a much lower risk of going to the hospital for heart failure or dying after they started weight-loss drugs, compared to high-risk people who were not on these medicines.
But his research also found that most patients stayed on the drugs for only around half a year. Some struggled with side effects; some faced insurance hurdles and cannot afford the medication.
These drugs are effective only if the medical system can get them to patients most in need, doctors stressed.
“The science is profound,” Dr. Yancy said. “Now we have to work on the public health.”
Dani Blum is a health reporter for The Times.
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