Weight regain after GLP1s – can it be stopped?

Hitting the headlines a couple of weeks ago now, the BMJ published a paper examining weight regain after cessation of medication for weight management. Although ostensibly looking at all weight loss medications, the key interest was on the newest incretin-based treatments: semaglutide and tirzepatide. 

For the 2 million plus private UK users, the question with these medications is no longer whether they can help people lose weight – the data is very clear they are very effective for a significant proportion of those who can tolerate them - the question is what happens if you stop? 

The new BMJ paper is a systematic review and meta-analysis aiming to quantify and compare weight regain after cessation of weight management medications in adults with overweight and obesity.  It examined studies including RCTs, non-randomised trials and observational studies which reported on weight change after cessation of weight management medicines for at least 4 weeks. 37 relevant studies were identified with >9000 participants. 

The key findings were no surprise – people regain weight after stopping the intervention. We have seen this already in trials, in our patients, our friends and family, and, very possibly, ourselves, regardless of whether weight loss is driven by medication, diet or lifestyle measures. 

The degree of weight regain observed is still disappointing: when looking at all weight management medications, on average people return to their baseline weight within an average of 1.7 years of cessation, with an average monthly rate of weight regain of 0.4kg. 

This regain is faster with semaglutide and tirzepatide – it seems the more weight you lose in the first place, the quicker you put it back on, and may be more likely to ‘over-shoot’ that initial weight. This contrasts with weight lost through non-pharmacological interventions or placebos, which were nowhere near as impressive in absolute amounts compared to the new medications, but demonstrate a much slower rate of weight regain. 

Where does this leave patients? What can we advise them if they ask about how, when or whether to stop these treatments? 

Firstly, we need to appreciate obesity is a chronic and relapsing condition (the UK, unlike many other countries, currently does not formally class obesity as a disease). As the linked opinion piece in the BMJ notes: “the obvious solution is to continue treatment”, just like we do for managing other long-term conditions such as hypertension or diabetes. 

There are two main barriers here for patients (and the NHS…). The first is cost. The second is side effects. Around 50% of people will stop incretin-based medications within 1 year of starting. 

It is difficult for clinicians to advise on how to mitigate these issues given the lack of data to guide us. 

Lower doses may be sufficient to maintain weight loss, reduce the risk of side effects and are typically cheaper than higher doses. Patient forums also describe extending the duration between injections as a potential strategy, although clinicians are unable to recommend this as manufacturer guidance is to not use tirzepatide after 30 days from the initial dose and semaglutide after 6 weeks.

There may be hope on the financial front for UK private users. Semaglutide is coming off patent in many countries in 2026. While buying medication from abroad is not advisable, generics elsewhere may indirectly reduce prices in other countries. UK patent expires in 2031 for semaglutide with tirzepatide to follow in 2032.

That feels like a long way off but in 2026 we may see the rise of oral GLP1ras, with semaglutide already available as Rybelsus, but also orforglipron, a new GLP1ra which is meant to be easy to make (so may be cheaper) and take (due to it being a small rather than large molecule like semaglutide). It is currently not licensed in the UK but with positive data for weight loss management and type 2 diabetes now published, a 2026 release may be possible.

Non-drug options would still be preferrable for many. However, it is clear that whatever the participants were doing for themselves after trial end does not work (at least on average…). The BMJ reported it found no evidence that behavioural support during the treatment phase improved weight maintenance after cessation. 

One trial, published in 2024, may provide some hope. It found that after dietary weight loss (using very low calories diets with rapid weight loss of around 10-15% of body weight) that regular exercise could substantially slow weight regain, including when liraglutide (a GLP1ra) had been used for a year post-diet as an adjunct for weight maintenance. Two hours per week of exercise that makes you moderately out of breath (‘panting’) achieved these benefits, with a substantial amount of weight loss still maintained at 2 years.

It is very welcome that weight regain after GLP1ra cessation has been widely reported in the popular press. People need all the facts when they are considering an intervention. There is one more, very important issue, that wasn’t reported in this paper: where does the weight loss come from? But this is a discussion for another day, one we will be covering this on the Spring/Summer 2026 Hot Topics course – find upcoming dates on www.nbmedical.com.