Study finds weight returns more quickly in GLP-1 users

 People who use drugs like GLP-1 agonists to lose weight regain it more quickly than those who use a conventional approach of diet and exercise, according to a new study.

The finding comes from an observational meta-analysis, published in the British Medical Journal, which evaluated 37 studies including more than 9,000 adults to assess how quickly weight is put back on after stopping obesity drugs.

It looked at older therapies like orlistat, which prevent fat from being absorbed from the diet, as well as massively popular GLP-1 agonists, Novo Nordisk's Wegovy (semaglutide) and Eli Lilly's Mounjaro/Zepbound (tirzepatide), which suppress hunger.

Overall, it found that patients could lose up to a fifth of their body weight using the injectable GLP-1s, but put it back on at a rate of 0.8 kg a month after the treatment stopped, which means that they should return to their former weight in as little as 18 months.

For all medicines, the average regain rate was 0.4 kg per month, according to the authors, and it happened up to four times faster compared to people who shed weight using behavioural weight management programmes, where the rebound occurred at around 0.1 kg a month and took an average of around four years.

Secondary benefits of the drug treatment, such as blood pressure and cholesterol levels, also returned to pre-treatment levels within 1.4 years.

"In summary, what we've shown in this particular piece of analysis is that weight regain after medication is common and is rapid," said Dr Susan Jebb of Oxford University, one of the study investigators.

"The cardiometabolic benefits essentially parallel weight – and so, as weight is regained, the cardiometabolic benefits are lost," she added.

One factor behind the rapid regain is that GLP-1s allow people to lose so much weight in the first place, they added, whilst also pointing to a high discontinuation rate with the drugs. They also suggested that behavioural methods encourage lifestyle changes that continue to be adhered to even as their weight starts to return.

Experts said the findings lend data to the intuitive idea that relying on drugs alone, without lifestyle changes, is inadequate for long-term results.

"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," commented Dr Adam Collins, a nutrition expert at the University of Surrey, who was not involved in the study.

"As soon as you withdraw this GLP-1 'fix', appetite is no longer kept in check, and overeating is far more likely," he added. "This is further exacerbated if the individual in question has relied solely on GLP-1 to do the heavy lifting during weight loss. The key message this paper supports is that weight-loss drugs […] have arguably made weight loss very easy, but maintaining the weight loss is now a bigger challenge than ever."

Prof Naveed Sattar from Glasgow University pointed out that the study cannot evaluate whether short-term use offers lasting benefits, but said it is "plausible that being lighter for even two to three years due to short-term use of the medicines could help slow damage to joints or hearts and kidneys."

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