A year after stopping taking weight-loss drugs such as Ozempic or Wegoby, people regain 60% of the weight they lost on average, but beyond that the weight plateaus and some people manage to keep 25% of the weight they lost on treatment, say researchers at the University of Cambridge.
However, it is not clear whether the weight gain consists of both fat and muscle, or whether it consists primarily of fat. Previous research suggests that lean body mass, including muscle, may account for up to 40% of the total body weight lost during treatment.
More than 1 billion people worldwide live with obesity, which increases the risk of diseases such as type 2 diabetes, cardiovascular disease, and cancer. Weight loss can help reduce these complications, but it can be difficult to lose weight through diet and exercise alone.
In recent years, a new generation of weight loss drugs has emerged that targets a protein known as the glucagon-like peptide 1 receptor (GLP-1R). These drugs help control blood sugar levels and reduce appetite, and clinical trials have shown that they can lead to weight loss of 15 to 20 percent.
About half of patients who start taking these drugs stop using them within the first year. But three-quarters stopped after two years. This may be due to potential side effects and limited access based on insurance coverage policies and national prescribing guidelines.
A team of students from Trinity College, University of Cambridge, investigated the effects of drug withdrawal and modeled weight recovery trajectories over 12 months. Their discovery today e-clinical medicine.
The team first conducted a systematic review of existing scientific and medical literature to identify and summarize all relevant evidence. They followed this up with a meta-analysis that combined results from multiple studies to estimate the overall effect. This approach allowed researchers to draw more robust conclusions from studies that may not provide sufficient evidence on their own and, in some cases, may not be consistent with each other.
In total, the team examined 48 relevant studies, including 36 randomized controlled trials (RCTs) and 12 non-randomized studies.
Most of these studies only followed patients for a few weeks after discontinuing the drug, so the research team selected six RCTs (consisting of more than 3,200 people in total) that followed patients for up to 52 weeks after discontinuing the weight-loss drug. They used these to model weight gain trajectories, including estimates beyond 52 weeks.
This model estimated that when an individual stopped taking the drug, weight would initially be regained quickly, and then recovery would slow over time. By 52 weeks, subjects had recovered 60% of their original loss.
At 60 weeks, weight regain is expected to begin to plateau and taper off at 75% of original weight loss. This means that 25% of your initial weight loss may be maintained long-term. For someone who lost a fifth of their body weight while taking the drug, this equates to a sustained weight loss of about 5%.
Weight recovery trajectories appeared to be similar for different classes of weight loss drugs that target GLP-1R.
Medications like Ozempic and Wigoby act like a brake on your appetite, making you feel full faster, so you eat less and lose weight. When you stop taking it, you are essentially taking your foot off the brake, which can lead to rapid weight gain. ”
Brajan Budini, Clinical Medicine Student, University of Cambridge
Researchers say there are several reasons why a person may not regain their original weight a year after stopping the drug. One reason is that by suppressing appetite, these drugs may help people develop healthier eating habits, such as smaller portion sizes and more nutritionally balanced meals, and these habits may persist even after treatment has stopped. Drugs can also have long-term effects on the body, changing hormone levels and “resetting” the brain’s appetite control mechanisms.
“When discontinuing weight loss drugs, doctors and patients need to be aware of the possibility of weight regain and consider ways to reduce this risk,” said Stephen Luo, also a medical student at the School of Clinical Medicine and Trinity College.
“It’s important to get advice on improving your diet and exercise, rather than relying solely on medication. This may help you maintain good habits even after you stop taking your medication.”
There is great concern about the long-term effects of GLP-1R drugs on body composition, with studies showing that 40-60% of the weight lost during treatment is muscle. It is unclear whether individuals will regain both fat and muscle.
Budini added: “Our predictions show that people will regain most of the weight they lost and still keep some of the weight they lost. But what we currently don’t know is whether they will regain the same proportion of lean body mass. If the weight they regain is disproportionately heavier, they may end up with a worse fat-to-lean body mass ratio than before, which could have negative health effects.”
The researchers say their study has several limitations. Most importantly, the trial data used to fit their model only extended to 52 weeks after discontinuation. They also limited their analysis to studies that reported an average weight loss of at least 3 kg during treatment.
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Reference magazines:
Budini, B. Others. (2026). Trajectories of weight recovery after discontinuation of GLP-1 receptor agonists: A systematic review and nonlinear meta-regression. EC clinical medicine. DOI: 10.1016/j.eclinm.2026.103796. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(26)00043-X/fulltext.
