In February 2021, a scientific paper came out that caused a sensation in the world of obesity research. It detailed the first results from studying weekly injections of the drug semaglutide—the generic name for Ozempic or Wegovy—to treat obesity. The paper showed that people taking the drug lost on average 15 percent of their body weight—a level of weight loss practically unheard-of for an anti-obesity medicine.
The paper, and the subsequent approval of Wegovy for weight management, kicked off an unprecedented clamor for this new generation of drugs. Demand for the injectables is so high that in May 2023, Wegovy manufacturer Novo Nordisk paused television advertising in order to buy itself time to produce more of the drug. Semaglutide is also used to treat type 2 diabetes, and in the UK patients have found it difficult to access the drug as Novo Nordisk struggled to keep up supply.
As demand for the drugs has risen, some have pointed out that for people to keep the weight off, they will likely have to stay on these drugs forever. That’s not surprising—the same is true for other weight loss interventions—but it raises a potentially vexing problem. The data we have suggests that a significant number of people stop taking these drugs after relatively short spans. We might have near-miraculous weight loss drugs, but what happens to the people who can’t stay on them?
These new drugs are part of a group called GLP-1 receptor agonists (GLP-1 RAs). They work by mimicking a hormone that regulates blood sugar levels and suppresses appetite by slowing down the rate at which food leaves the stomach. While using them to treat obesity is pretty novel, they’ve been approved for type 2 diabetes for a while. The first GLP-1 RA was approved by the US Food and Drug Administration in 2005. That means we have some decent real-world data about how long people stay on GLP-1 RAs and the reasons they quit them.
One study looked at GLP-1 RAs prescribed in the UK between 2009 and 2017. Out of the 589 patients who started taking a GLP-RA, 45 percent stopped taking the drug within 12 months, and 65 percent within 24 months. The same group of scientists also looked at people taking GLP-1 RAs in the US across a similar period of time. That study included a much larger group of diabetes patients but found that people quit taking the drugs at a similar rate as in the UK. Within 12 months, 47 percent of patients stopped taking their GLP-1 AR; after 24 months that figure was 70 percent. On average, people in that study spent around 13 months using the drug before they stopped taking it.
Other real-world findings paint a similar picture. About half of Spanish patients taking a GLP-1 RA had stopped taking the drug after two years—a higher dropout rate than for other diabetes drugs. In Denmark, around 45 percent of diabetes patients stopped taking GLP-1 RAs within five years of starting the therapy, although a quarter of them started again within the following year. In lots of these studies, the scientists note that people quit these drugs at much higher rates than they do during clinical trials.
That isn’t surprising, says John Wilding, an obesity researcher at the University of Liverpool who led a major study on the use of semaglutide to treat overweight or obese adults. “Clinical trials tell us about the biology–whether the drug works—and it’s a very highly controlled situation because that’s the way the trials are designed,” he says. People don’t usually have to pay for drugs in clinical trials, and they’re supported with regular check-ins from research staff.
In the real world, there are all kinds of reasons people stop taking drugs. One survey of diabetes patients asked them—and their doctors—why they stopped taking their GLP-1 RA. Patients who quit the drugs cited side effects such as nausea and diarrhea, disliking having to inject themselves regularly, and disappointment that the injections didn’t help them lose weight or control their blood glucose. In the US, almost half of patients who stopped taking a GLP-1 RA cited high costs as a reason. We know that patients in the US who have higher insurance copayments are less likely to stick with their diabetes medicine. “These drugs are wildly expensive, especially the weekly ones,” says William Polonsky, president of the Behavioural Diabetes Institute in California. The list price for a monthly dose of Wegovy is almost $1,350, although some insurers cover at least part of that hefty cost.
If these patterns hold true for the drugs as they are used for weight loss—and that’s still a big “if” at the moment—then maybe we shouldn’t expect that everyone who starts taking Wegovy or similar drugs will stay on them forever. The UK’s National Institute for Health and Care Excellence, which decides which drugs should be available through the National Health Service (NHS), recommends a two-year cap on how long someone can be prescribed Wegovy for weight loss. It’s possible, Wilding says, that some people will stop taking the drug after they’ve lost a certain amount of weight and opt to manage their health through diet and exercise instead.
We already know that when people stop taking semaglutide, they regain most of the weight they lost during the treatment. This raises an important question. If people regain their lost weight, are they still healthier in the long run than someone who never lost the weight in the first place?
For semaglutide, the short answer is that we don’t know. But there is some intriguing data that suggests dietary interventions can have lasting benefits long after they’ve been dropped. In 1986, nearly 440 prediabetic people in the Chinese city of Da Qing were assigned to a trial in which they were encouraged to follow a healthier diet, exercise, or a combination of the two for six years. The control group was asked to continue their lifestyle as normal. Thirty years later, scientists returned to the people who had taken part in the study and found that those in the diet and exercise groups had later diabetes onset and less cardiovascular disease than people in the control group.
The Da Qing research didn’t study weight loss directly, but it does suggest that even a relatively short time spent following an intervention might have long-lasting benefits. Wilding says that people who take a GLP-1 RA for a few years and then stop might end up healthier than if they’d never taken the drug. “It may be that you buy some future health. Probably not as much as if you continued to take it, but nevertheless there may be some residual benefit.”
It could also be the case that as these new weight loss drugs improve, people stay on them longer. Many of the early GLP-1 ARs required daily injections, but Wegovy, Ozempic, and Mounjaro are all weekly injections. Drug companies are also racing to make pill versions of the weight loss drugs, as some patients are put off by having to inject themselves regularly. In May, Novo Nordisk announced that a semaglutide pill helped people achieve weight loss levels similar to the injectable version.
“Convenience drives behavior,” says Polonsky. If manufacturers can make drugs that are cheaper and easier to administer, then people will likely stay on them longer. There’s also another reason to think that adherence rates for weight loss might be higher than for diabetes—people who are using GLP-1 RAs to lose weight can usually tell quite quickly whether the drug is working for them. That positive feedback might make them more likely to stick with the drug, even if they’re struggling through side effects.
This short-term feedback could be the route to long-term health benefits. Although we know that semaglutide helps people lose weight, there aren’t yet any big clinical trials to tell us whether this weight loss leads to reductions in heart disease and stroke—two conditions that are strongly linked to obesity. In June, a big trial investigating whether semaglutide reduces rates of cardiovascular disease finally wrapped up after five years and 17,609 participants. When those results are published, they will shed light on whether these drugs improve people’s long-term health, as well as helping them lose weight. If the results are positive, it could make demand for these already sought-after medications even greater.
