Medications such as Ozempic and Wegovy have transformed the landscape of obesity treatment, helping many people lose significant amounts of weight by reducing appetite and slowing digestion.
But what happens when people stop taking them?
A new systematic review and meta-analysis published in eClinicalMedicine and led by researchers at the University of Cambridge suggests that weight regain is common after discontinuing these medications, though not all of the lost weight returns.
Analyzing data from dozens of studies, the researchers estimated that people regain about 60% of the weight they lost within a year of stopping GLP-1 receptor agonist drugs. After that initial rebound, weight regain appears to slow and eventually level off.
Over the longer term, the model suggests individuals may maintain about 25% of their original weight loss.
GLP-1 receptor agonists mimic a hormone involved in appetite regulation. By helping people feel full sooner and reducing hunger signals, the medications can lead to substantial weight loss. Clinical trials have found that some patients lose 15% to 20% of their body weight while taking the drugs.
“When people stop taking them, they are essentially taking their foot off the brake, and this can lead to rapid weight regain,” said Brajan Budini, a medical student at the University of Cambridge and one of the study’s authors.
To better understand what happens after treatment ends, the research team conducted a systematic review of the scientific literature and identified 48 relevant studies, including 36 randomized controlled trials and 12 non-randomized studies.
Many of those trials only tracked patients for a short period after they stopped taking the medication. To examine longer-term patterns, the researchers focused on six randomized trials that followed more than 3,200 participants for up to 52 weeks after discontinuation.
Using those results, they modeled how body weight changes over time once treatment stops.
The analysis found that weight regain tends to occur rapidly at first, then slows over time. By about 52 weeks after discontinuation, participants had regained roughly 60% of the weight they had lost while taking the drugs.
Beyond that point, the trajectory begins to flatten. The researchers estimated that weight regain eventually plateaus at about 75% of the original weight loss.
In practical terms, someone who lost 20% of their body weight during treatment might ultimately maintain a reduction of roughly 5%.
The researchers said several factors may help explain why some weight loss persists even after the medications are stopped.
Budini said the drugs may give people time to adopt healthier eating patterns that continue after treatment ends.
“It’s important that people are given advice on improving their diet and exercise, rather than relying solely on the drugs, as this may help them maintain good habits when they stop taking them,” he said.
Another possibility is that the medications produce longer-lasting changes in appetite regulation or hormone signaling that continue to influence eating behavior after treatment.
However, the researchers noted important unanswered questions about body composition.
Previous research has suggested that 40% to 60% of weight lost on GLP-1 medications may come from lean mass, including muscle. The new analysis could not determine whether the weight regained after stopping the drugs consists primarily of fat, muscle or a combination of both.
If the regained weight consists mostly of fat, the researchers say it could affect long-term metabolic health.
The study also has limitations. Most of the available clinical trials only followed participants for about a year after they stopped treatment, meaning longer-term outcomes remain uncertain.
Still, the results suggest that while GLP-1 medications can produce substantial weight loss, maintaining those changes may require ongoing treatment or sustained lifestyle changes.
The researchers reported that the study did not receive external funding.