Results from the longest-running trial of semaglutide—the active ingredient in the popular drugs Ozempic and Wegovy—are in, and the verdict is decidedly positive. The study found that people taking semaglutide tended to maintain their initial weight loss for up to four years. Other trial data presented this week also suggests that semaglutide can improve people’s heart health even without causing weight loss.
Last summer, the makers of semaglutide, Novo Nordisk, reported the main findings of the SELECT trial. The trial involved over 17,000 people and tested whether the drug could help overweight or obese individuals without diabetes but with pre-existing cardiovascular disease. The trial found that high-dose semaglutide cut the risk of major cardiovascular events by 20% for up to five years when compared to a placebo.
The new research, published Monday in Nature Medicine, specifically analyzed the weight loss outcomes of those in the SELECT trial. On average, people taking semaglutide lost about 10% of their baseline weight within 65 weeks, far more than those on placebo, according to the study. By year four, these results remained remarkably consistent, with an average 10.2 percent weight loss seen in patients still taking the drug.
“These data, representing the longest clinical trial of the effects of semaglutide versus placebo on weight, establish the safety and durability of semaglutide effects on weight loss and maintenance in a geographically and racially diverse population of adult men and women with overweight and obesity but not diabetes,” the authors of the Nature Medicine paper wrote.
The results are somewhat less impressive than other clinical trials of high-dose semaglutide, which have shown outcomes hovering around 15 percent weight loss on average. And not everyone taking the drug in the trial lost significant weight or necessarily maintained their weight loss four years later. But the data does indicate that semaglutide and other related GLP-1 drugs generally can be taken over the long haul without losing their potency or causing serious problems.
GLP-1 drugs are known to cause common gastrointestinal side effects such as vomiting and diarrhea, though some data has suggested that these side effects become less common over time. And in the SELECT trial, the risk of serious adverse events after four years was actually lower in the semaglutide group than placebo—likely due to the drug’s effects on improving cardiovascular health, the authors say.
Obesity can raise people’s risk of cardiovascular disease, and it’s likewise thought that much of the heart benefit provided by these drugs comes from helping people lose clinically significant amounts of weight and body fat. But another analysis of the SELECT trial presented this week, at the European Congress of Obesity, suggests that things are more complicated than that. This study found that people on semaglutide tended to experience fewer cardiovascular events no matter their starting weight or if they lost much weight at all.
“Our findings show that the magnitude of this treatment effect with semaglutide is independent of the amount of weight lost, suggesting that the drug has other actions which lower cardiovascular risk beyond reducing unhealthy body fat,” said John Deanfield, a researcher from University College London who led the second study, in a statement from the European Association for the Study of Obesity. “These alternative mechanisms may include positive impacts on blood sugar, blood pressure, or inflammation, as well as direct effects on the heart muscle and blood vessels, or a combination of one or more of these.”
The results of both studies are likely to bolster attempts to expand insurance coverage of these drugs, which are expensive and often not covered by private or public payers.
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