Weight regain seems to occur within 2 years of stopping obesity drugs

People who stop taking weight-loss drugs tend to regain the weight they lost within less than two years, according to a study of more than 9000 people. Some argue that this emphasises that obesity is a chronic condition that requires long-term treatment.

“These drugs are highly effective but obesity is a chronic, relapsing condition,” Susan Jebb at the University of Oxford said at a press briefing. “One would expect that these treatments need to be continued for life, just in the same way as blood pressure medication.”

Weight-loss drugs have undoubtedly helped to tackle obesity. This is particularly the case for newer GLP-1 medications – which mimic a gut hormone called glucagon-like peptide-1 – such as semaglutide, sold as Ozempic and Wegovy, and tirzepatide, sold as Mounjaro and Zepbound. Such drugs also impact our health in other ways, such as by lowering blood pressure and cholesterol levels.

But many people come off GLP-1 drugs due to side effects such as nausea or because of supply shortages following soaring demand. “Around half of people discontinue these medications within a year,” said Jebb.

Moreover, while many countries, including the US and some in Europe, enable long-term use of GLP-1 drugs, the National Health Service in England, for example, caps the use of semaglutide for weight loss at two years, based on estimates of its cost-effectiveness.

Prior studies show that people tend to regain weight when they come off semaglutide. However, whether this applies to stopping weight loss interventions more broadly, and how quickly any weight gain occurs, was less clear.

To find out, Jebb and her colleagues analysed 37 trials that tracked the weight of more than 9000 people altogether. The individuals were either overweight or had obesity and they took some form of weight-loss medication, including GLP-1 drugs, for an average of 10 months. The participants were then tracked over a follow-up period of around eight months.

When combining the effects of all the weight-loss drugs, the researchers found that the participants lost 8.3 kilograms, on average, and also saw improvements in metabolic measures, such as blood pressure, cholesterol levels and blood glucose levels.

The team then fed weight measurements from the follow-up periods into a statistical model, and estimated that, on average, the participants would have regained all the weight they lost within 1.7 years after they stopped taking the various medications.

When focusing on six trials involving semaglutide and tirzepatide, the researchers found that these drugs led to greater weight loss than other medications – at 14.7 kilograms, on average – but the participants taking these drugs were expected to regain all their lost weight within 1.5 years. Further research is needed to establish why weight gain seems to be faster with these drugs than others, said Jebb.

The team also calculated that the rate of weight regain after discontinuing weight-loss medications is roughly four times faster compared with that seen after people come off a structured behavioural weight-loss programme, where they are encouraged to eat healthily and exercise more, and then have to incorporate this into their life.

However, the difference between these interventions could simply be because people who sign up to such a behavioural programme may be more motivated to lose weight than those who set out to do so using a drug.

Another reason for the difference in the speed of weight regain could be that people who take such medications mainly lose weight due to the drugs suppressing their appetite. Coming off them then quickly increases people’s hunger and cravings, which they haven’t had to deal with for a while, potentially leading to faster weight gain, says Taraneh Soleymani at the Pennsylvania State University.

Still, another analysis by the team revealed that providing behavioural support during the studies’ follow-up periods didn’t prevent weight gain. Further studies are needed to understand how best to support those who discontinue weight-loss drugs, says Soleymani.

What Jebb’s study does show, she says, is the importance of treating obesity as a long-term condition. “We know weight-loss medications are effective, and that weight regain is common when you stop taking them,” says Soleymani. “What these findings do is support the fact that obesity is a chronic condition, and we have to keep patients on treatments long term.”