Many people who come off GLP-1 drugs regain weight within 2 years, review suggests

By Jack Guy, CNN

(CNN) — Many people who stop using weight loss drugs will return to their previous weight within two years, a new review of existing research has found.

This rate of weight regain is significantly faster than that seen in those who have lost weight by changing other lifestyle factors, such as diet and exercise, rather than relying on GLP-1 medications, researchers from the University of Oxford report in a paper published Wednesday in The BMJ journal.

GLP-1, which stands for glucagon-like peptide-1, is a hormone naturally made by the body that helps signal to the brain and the gut that it’s full and doesn’t need to eat any more.

Weight loss drugs mimic the action of this hormone by increasing the secretion of insulin to lower blood sugar.

They also slow the movement of food through the digestive tract, which helps people feel full more quickly and for longer, and they work in the brain to reduce appetite.

GLP-1 medications, which include Ozempic, Wegovy, Mounjaro and Zepbound, have proven to be highly effective for weight loss.

However, University of Oxford researchers analyzed the results of 37 studies involving more than 9,300 adults.

They found that “weight regain after stopping drugs was faster than after ending behavioural weight loss programmes such as diet and exercise support by approximately 0.3 kg (0.7 pounds) per month,” they said in a statement.

“This isn’t a failing of the medicines — it reflects the nature of obesity as a chronic, relapsing condition,” said study lead author Sam West, a postdoctoral researcher at the Nuffield Department of Primary Care Health Sciences, University of Oxford, in the statement.

“It sounds a cautionary note for short-term use without a more comprehensive approach to weight management.”

Overeating ‘far more likely’

Adam Collins, associate professor of nutrition at the University of Surrey in England, who was not involved in the study, called the paper “timely and important.”

Collins underlined that weight regain is a common issue in all weight loss interventions, but the paper shows that this problem is amplified with GLP-1 medications.

Collins also offered some possible explanations as to why this is the case.

“Artificially providing GLP-1 levels several times higher than normal over a long period may cause you to produce less of your own natural GLP-1, and may also make you less sensitive to its effects,” he said in a statement shared with CNN by the Science Media Centre.

Collins added that this isn’t a problem when taking these drugs, but taking away this source of GLP-1 then makes overeating “far more likely.”

“Like any addict, going cold turkey is a real challenge. This is further exacerbated if the individual in question has relied solely on GLP-1 to do the heavy lifting during weight loss,” he said, rather than making behavioral changes.

Long-term conclusions rely on extrapolation

Marie Spreckley, obesity researcher and public health nutritionist at the University of Cambridge in England, who was not involved in the study, cautioned that the paper’s long-term conclusions rely on modeled projections, rather than observed data, as the follow-up period for stopping treatment with newer medicines is limited to about 12 months.

“As a result, longer-term statements, including full weight regain within two years, rely on extrapolation beyond the available data,” she said in a statement shared with CNN by the Science Media Centre, meaning that comparisons with behavioral changes should “be interpreted as suggestive rather than definitive.”

“In real-world terms, the findings reinforce that obesity management typically requires long-term planning. If people stop medication, many are likely to need ongoing nutritional and behavioural support, and health services should anticipate that cardiometabolic benefits may lessen as weight is regained,” Spreckley said, adding that this highlights “the need for further research into effective, scalable strategies for long-term weight maintenance alongside pharmacotherapy.”

GLP-1 medications have become widely used in recent years, and more than 15 million Americans are now losing weight with the drugs.

And a study published in January 2025 suggested that popular GLP-1 medications approved for weight loss, diabetes and heart disease may have untapped potential to reduce the risks of substance abuse disorders, psychosis, infections and some kinds of cancer and dementia.

However, it is important to remember that using the drugs to suppress appetite doesn’t just contribute to fat loss but also to reduced muscle mass.

Studies have indicated that anywhere between 15% to 60% of the weight people lose is lean muscle mass, meaning that those who are using the drugs are advised to engage in a weekly exercise routine that includes strength training to stave off too much muscle loss.

It is particularly important for those 65 or older, who are already at risk of age-related loss of muscle mass, strength and function.

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Melanie Radzicki McManus and CNN’s Brenda Goodman contributed to this report.