Glucagon-like peptide-1 receptor agonists (GLP-1s) were developed as treatments for patients with type 2 diabetes. But in November 2009, a study published in The Lancet showed that after 20 weeks of once-daily injections of the GLP-1, liraglutide, overweight and obese patients without type 2 diabetes lost up to 7.2kg. This was the first evidence that this class of drugs could aid weight loss.  

Although further trials confirmed these findings, the appetite for using GLP-1 rugs for weight loss only came to prominence in 2021, following the publication of a trial with another agent, semaglutide. This 68-week trial observed that among those assigned to semaglutide plus diet and exercise, an average of 15.3kg was lost compared to 2.6kg with placebo.  

By 2023, NICE had approved the drug class, together with tirzepatide (which targets an additional gastrointestinal receptor related to satiety), for weight loss. Since then, the use of these drugs has skyrocketed – largely because of increased exposure and celebrity endorsement on social media.  

According to data from a King’s Fund report, more than 800,000 GLP-1 items were prescribed in 2025, compared to around 100,000 in 2020. In addition, many patients have obtained the drugs privately through online pharmacies or community pharmacy weight loss services. The current value of the GLP-1 market is huge, with 2025 estimates of $62.2bn and projections to reach $157.5bn by 2035.  

Despite the widespread use of these drugs, studies have found that discontinuation rates are high. One recent analysis of nearly 49,000 patients initiated on a GLP-1 without type 2 diabetes found that 64.8 per cent stopped the drug within 12 months. The key reasons for discontinuation were side effects and drug costs. 

But what happens once a drug is stopped, and more importantly, does the weight return?

Latest findings 

In 2022, the findings of an extension to the STEP1 trial were published. In STEP1, the use of semaglutide in combination with exercise and diet led to average weight losses of 17.3 per cent after 68 weeks of treatment. The extension followed patients who had completed the initial 68 weeks for a further 12 months. 

Researchers observed that 12 months after stopping semaglutide, participants regained 11.6 per cent of their weight loss. In other words, the net weight loss was 5.6 per cent. Furthermore, improvements in cardiometabolic health, such as lower blood pressure and HbA1c, were reversed.

But the STEP1 extension was only one trial: what about the others? 

A recent meta-analysis published in the BMJ shed further light on the degree of weight regain once GLP-1s were stopped. The analysis included 37 studies with 9,341 participants, who used a GLP-1 for an average of 39 weeks. The results showed that the average monthly rate of weight regain was 0.4kg and that an individual’s weight would return to its original value after 1.7 years.

In addition, all favourable cardiometabolic changes were projected to return to baseline levels 1.4 years after stopping treatment. Quite why stopping these drugs leads to rapid weight regain is unclear. However, given that the drugs boost satiety and reduce appetite, individuals are probably less likely to rely on cognitive strategies to curtail their appetite, and therefore less likely to be able to manage their weight when treatment ends. 

How practice might change  

Given these findings, the initial enthusiasm for the GLP-1s has been tempered. Although weight loss improves cardiometabolic health, perhaps it is more important to view overweight and obesity as a chronic, relapsing-remitting condition. 

When viewed in this context, the stigma associated with obesity might subside as it becomes regarded more as a disease that requires pharmacological treatment. Nevertheless, the latest meta-analysis has shown that GLP-1s are insufficient to ensure long-term weight maintenance. 

Equally important is that patients are provided with all the necessary information prior to starting treatment to enable them to make an informed decision. Interestingly, one US survey found that while just under half (45 per cent) of adults would be interested in taking a safe and effective weight-loss drug, this interest dropped to just 14 per cent when they were informed that weight regain would occur upon stopping the drug.  

The recent guidance from the World Health Organization (WHO) has recognised that GLP-1s alone are not a solution to the global obesity crisis. The WHO suggests a strategy that creates healthier environments, protects individuals at high risk of obesity through targeted screening, and ensures access to lifelong, person-centred care. But conversely, given the widespread use of GLP-1 drugs, there is a risk that focusing solely on these agents could distract from efforts directed towards obesity prevention. 

Shift of focus 

Given the scale of the obesity problem and the substantial healthcare costs associated with the widespread implementation of GLP-1s, it is abundantly clear that these agents will not become universally available. In other words, while recognising obesity as a chronic disease might reduce weight stigma, using pharmacological approaches alone for obesity management could shift the emphasis away from an overhaul of the current obesogenic food environment that encourages overconsumption. 

Nevertheless, preventative and treatment strategies for obesity are not mutually exclusive. For example, a recent study that compared patients using GLP-1s to non-users observed how people those taking these drugs consume significantly fewer calories. In addition, GLP-1 users were less likely to eat processed foods, sugar-sweetened beverages, refined grains, and beef.  

Thus, while the GLP-1 drugs clearly have an important role in obesity management, greater emphasis is required to encourage dietary and exercise modifications to ensure that the dramatic initial weight losses are maintained.