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A new study looked at how long people taking the GLP-1 Wegovy maintained their weight loss. Maskot/Getty Images
  • People receiving weight-loss drug Wegovy (semaglutide) lost an average of 10% of their body weight after four years, a clinical trial found.
  • Study participants lost weight during the first year and three months of the study, after which their weight plateaued.
  • A new analysis of data from the study found that people saw cardiac benefits of semaglutide regardless of how much weight they lost.

People receiving weight-loss drug Wegovy (semaglutide) sustained weight loss for up to four years, shedding an average of 10% of their body weight during that time, a new study found.

This is the longest clinical trial to date of this drug, which belongs to a class of medications known as GLP-1 receptor agonists.

The study, known as the SELECT trial, included over 17,000 adults who had obesity or overweight but did not have diabetes. People stayed on the medicine throughout the clinical trial.

The findings also suggest that there are heart health benefits in addition to those related to weight loss.

“At four years, we see ongoing benefits [of semaglutide],” said Cheng-Han Chen, MD, interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, Calif., who was not involved in the research.

Not only do “patients continue to have a reduction in weight, but also, more importantly, they continue to have a reduction in cardiovascular outcomes,” he told Healthline.

The study was published May 13 in Nature Medicine.

Overall, people who received once-weekly injections of semaglutide lost on average 10.2% of their body weight over the course of four years. Study participants continued to lose weight for about 65 weeks — a year and three months — and then their weight remained at a stable level.

However, people’s experience with the medication varied.

Of the people on the highest dose of Wegovy, 68% lost at least 5% of their body weight. This compared to 21% of people on the placebo.

Additionally, of the total people on Wegovy about 23% lost at least 15% of their body weight. For those in the placebo group, only 1.7% lost that much body weight.

An earlier clinical trial showed that people receiving semaglutide lost on average almost 15% of their body weight over 68 weeks, compared to only 2.4% in people who got a placebo. That trial was designed to test the drug’s effect on weight loss, and it also included structured diet and exercise interventions.

In contrast, the SELECT trial was designed to see whether semaglutide prevented cardiovascular events such as heart attack and stroke, and did not include lifestyle interventions. This may explain the lower amount of weight loss in the SELECT trial.

Mir Ali, MD, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, Calif., said the new trial verified the safety profile of semaglutide, showing “fewer side effects” of the drug than originally thought.

Researchers found no unexpected safety issues with the drug during the trial.

In addition, the most common reasons that people receiving semaglutide withdrew from the trial were gastrointestinal symptoms such as nausea and diarrhea, which are known side effects of the drug. This occurred mainly during the beginning of the study, as the dose of the medicine is increased to a maximally tolerated dose.

The rate of serious adverse events was lower among people receiving semaglutide (33%) compared to the placebo group (36%). This was mainly due to lower rates of major cardiovascular events among people in the semaglutide group.

Rates of inflammation of the pancreas (pancreatitis) were similar in both groups, but rates of gallstones were higher in the semaglutide group. Both of these have been seen in earlier trials, and are included as a warning in the medication’s prescribing information.

An analysis last year of the SELECT trial data found that semaglutide significantly reduced the risk of heart attack, stroke, and cardiovascular-related death in adults with obesity or who are overweight.

This led to the Food and Drug Administration approving Novo Nordisk’s Wegovy for reducing the risk of heart-related events in this group of people.

A new analysis of trial data suggests that the heart-related benefits of the drug extend beyond weight loss — even people who didn’t lose weight while on the drug had a lower risk of heart attack, stroke, and other events, researchers found.

That analysis, which was presented May 13 at the European Congress on Obesity, shows that “patients may benefit from [semaglutide] even if they are not significantly overweight,” Ali told Healthline.

“Some of the possible mechanisms [for this] are that the drug may be better [at] controlling blood glucose, improving cardiovascular status, or perhaps it’s reducing inflammation,” he said.

However, more research is needed to understand the mechanisms behind the heart-related benefits of the drug. Additionally, more research will be needed to see if people who have had a previous heart attack or stroke, but don’t have obesity, might also benefit from taking semaglutide.

Given the strong safety profile, the benefits of weight loss, and the heart-related benefits, now insurers have more reasons to cover GLP-1 drugs which have a list price of approximately $1,349 for a one-month supply.

Although this is the cost before insurance coverage, coupons or rebates, around half of people with insurance coverage still struggle to pay for GLP-1 drugs such as Wegovy, a recent KFF survey found.

The benefits may be worth the price, though.

“While this medicine is expensive, you’re preventing a lot of complications from cardiovascular disease down the road,” said Chen. “So from a public health perspective, it is very important that we provide this medication for patients.”

One question insurers may be wondering is whether they will have to continue paying for the drug indefinitely once people start taking it, as they often do with medications for lowering cholesterol and high blood pressure.

There is some research to suggest that ongoing treatment with GLP-1 drugs may be needed. Some studies have found that people regain some weight after they stop treatment. However, researchers have not yet examined whether any of the heart-related benefits persist if people go off the drug.

Ali said obesity is better thought of as “a chronic disease, like diabetes or high blood pressure, that may need long-term treatment,” rather than something that could be treated and then you’re done.”

And “with any treatment — whether it’s medication or surgery — the goal is to help the patient change to a healthier diet and lifestyle,” he said, “and then their weight loss results can be more sustainable.”

In a study of over 17,000 adults, researchers found that people receiving Wegovy (semaglutide) lost an average of 10% of their body weight after four years. People lost weight for the first 65 weeks of the study, after which their weight plateaued.

An earlier analysis of data from this trial found that semaglutide reduced the risk of heart attack, stroke and cardiovascular death in people with obesity or who are overweight. A new analysis found that these heart-related benefits occurred regardless of how much weight people lost.

This suggests that the benefits of semaglutide extend beyond weight loss. Researchers say the benefits may be due to the positive effects of the drug on blood sugar, blood pressure, inflammation or other factors.