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Stop the drugs, regain the weight

AFP – A new generation of obesity drugs often delivers dramatic weight loss, but many patients wonder what happens when they stop treatment.

One study published on in the Journal of the American Medical Association provides an answer: much of the weight comes back, signalling that patients may be locked into long-term dependence on the drugs.

The research was based on weekly injections of tirzepatide, a new weight-loss drug that was approved by the United States in November 2023.

After nine months, the 670 adults in the study achieved a notable average (mean) weight loss of 20.9 per cent.

The group was then split into two, with half continuing on the drug, and the other half given a placebo.

At 22 months, those on the placebo regained almost half of the weight they had lost, ending up 9.9 per cent lower than their baseline.

Those on tirzepatide continued to lose weight, ending 25.3 per cent lower than where they had started.

The study participants were mostly women and had an average (mean) age of 48, with an average (mean) weight at the outset of 107.3 kilogrammes.


All participants were encouraged to consume 500 calories less each day than they burnt and take at least 150 minutes of exercise per week.

Common side effects were gastrointestinal issues including nausea, diarrhoea, constipation and vomiting, the study found.

The study authors, led by Professor Dr Louis Aronne at Weill Cornell Medicine in New York, United States, said the results “emphasise the need to continue pharmacotherapy to prevent weight regain and ensure the maintenance of weight reduction”.

They added that the latest research adds to four previous trials that showed “medications, including potent anti-obesity medications such as semaglutide, have demonstrated that weight is substantially regained” after stopping treatment.

Both semaglutide and tirzepatide are examples of GLP-1 (glucagon-like peptide-1) agonists that work by mimicking the function of a hormone that secretes insulin, slows down the emptying of the stomach, and suppresses appetite.

Tirzepatide also contains another molecule that acts like the gut hormone glucose-dependent insulinotropic polypeptide (GIP).

In response to the study, Eli Lilly senior vice-president for product development Jeff Emmick said in a statement that “patients, providers and the public do not always understand that obesity is a chronic disease that often requires ongoing treatment, which can mean that treatment is stopped once weight goals are met”.

Eli Lilly is the American pharmaceutical company that manufactures tirzepatide.

GLP-1 agonists have been found to cut the risk of heart disease associated with obesity, but they also heighten the risk of gastrointestinal problems, studies show.

Though the rates of serious issues such as stomach paralysis are low, some experts fear that using the drugs for years or decades could change the benefit- to-risk calculus.