There has been nothing short of a seismic shift in the weight loss space since new weight management medications such as Mounjaro came on the scene.
You would have had to have been seriously not paying attention not to know this.
The drugs have dramatically altered the options for people living with obesity, and the success of the drugs has meant that people who don’t meet the NHS criteria for prescription have been clamouring for them.
Pause for a serious health message here – if you’re looking to buy any of these drugs privately, it’s vital to do this through a medical doctor or a reputable company that employs prescribing doctors, and not via unregulated sites on the internet. The health risks are way too serious.
How do they work?
No-one fully understands the mechanisms behind these weight management medications (WMMs). Listening to people who are taking the drugs, you hear of a dramatic change in their inner landscape around food, eating and appetite. Fullness feels different or comes sooner, they have reduced interest in food and a dramatic reduction in ‘food noise’ – a continual mental chatter involving food and eating.
We might not know the mechanism, but it is clear that the drug is affecting physical sensations associated with appetite, and mental processes involved in thinking about, finding and consuming food.
What sort of drugs are they?
As relatively new kids on the block, these medicines are a source of curiosity and intrigue. Are they a bit like other drugs we are more familiar with?
- Are they for example a bit like an antibiotic? If so, a course of treatment would correct the biological problem (bacterial infection in the case of the antibiotic; faulty appetite signalling in the case of WMMs) and when you got to the end of the course, you would be better and could discontinue the medication with the beneficial changes intact.
- Or maybe more like drugs for hypertension? Here, the drug corrects the underlying biological mechanisms (regulating blood pressure) whilst you are taking it, but if you discontinue it, the mechanisms governing your blood pressure revert to their harmful patterns. These drugs need to be taken over the long term to maintain healthy blood pressure.
- Or perhaps are they more like anti-depressants? Some people can take anti-depressants for a limited period, during which time the lift in mood and energy allows them to make changes – perhaps through psychological therapy – which then persist as the drug is tapered off.
Weight management medications are of course none of the above, but this might be a useful analogy for how they work.
Interestingly, I asked two highly experienced and expert colleagues who work in NHS specialist weight loss services what they thought was the best analogy. The obesity medicine physician, Dr Kenneally, said she thought blood pressure medication was the best analogy whilst Dr B, Consultant Clinical Psychologist, said she thought anti-depressants were a better illustration.
You may be hoping – assuming even – that your WMM will act like the example of the antibiotic – once you’ve had a course of treatment, your appetite will stay ‘fixed’ and your weight will remain stable. But what does the research show?
Outcomes
One indicator of how WMMs work is outcome studies on people who take, and then stop taking the medication. A recent systematic review* showed that while WMMs are undeniably effective in achieving initial weight loss, the data clearly indicate that their benefits are vulnerable to reversal once treatment is ceased.
The authors of this study say that this, “provides robust quantitative evidence that weight regain is not a treatment failure but a predictable biological response and must be anticipated and addressed in clinical practice. By reframing pharmacotherapy as a maintenance tool rather than a finite intervention, healthcare systems can better support patients in achieving sustained, long-term weight control and improved metabolic health.”
This study points towards the medication working more like blood pressure medication.
Another systematic review and meta-analysis of the literature** concluded that
- Real world observations estimate that around 50% of people with obesity discontinue WMMs within 12 months
- People on average regain weight at a rate of 0.4 kg/month after cessation of WMMs, leading to a projected return to baseline weight after 1.7 years
Again, a bit like blood pressure medication.
But this study also compare weight regain after WMM with data from a previous review of Behavioural Weight Management Programmes (BWMPs) assessing weight change to two years post-treatment. Weight loss at the end of BWMPs was on average 5.1 kg with an estimated monthly weight regain of 0.1 kg. On average, weight loss with WMM was 3.2 kg greater than that with BWMPs, but monthly weight regain was significantly faster after WMM than after BWMPs by 0.3 kg.
Body weight after BWMPs was predicted to return to baseline 3.9 years after the end of treatment, compared with 1.7 years after WMM. Larger initial weight loss led to faster weight regain for both WMM and BWMPs, and the rate of regain was consistently faster after WMM than after BWMPs. Perhaps integrating the two – approaching the treatment like incorporating psychological treatment and anti-depressant medication – will be most helpful for some people.
This opens a whole other question, of what would be helpful for the 50% of people who stop the medication within a year. And another of to what extent behavioural and psychological support during WMM treatment might reduce the risk of weight regain (as per the anti-depressant analogy). Following the massive success of these medications for many people, the million dollar question is becoming “what-else-is-needed?”.
Too early to tell
It is early days, and there’s so much to learn.
My own hunch, for what it’s worth, is that if you take WMM that significantly alters your appetite signalling while you’re taking it, you can only partly establish behavioural changes to how you’ll eat when you stop the medicine. I say that because as your appetite signals revert to how they are without the medication, you’ll feel less full, or more hungry, or the food noise may return.
In other words, the pressures on you to eat will be different. So I’m on the fence straddling hypertension and anti-depressant type descriptions.
You may be able to establish really helpful habits while you’re on the medication and your appetite signals are altered. And then aim to sustain some of these. But don’t beat yourself up if you can’t.
Of course it’s possible that WMMs may affect different people differently so that some people react as though it’s like an anti-hypertensive and some like an anti-depressant, and maybe even some who respond more like an antibiotic.
We are living in interesting times, with lots to learn.
References
* Kolli RT et al (2025) Rebound or Retention: A Meta-Analysis of Weight Regain After the Discontinuation of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Other Anti-obesity Drugs. Cureus. 2025 Oct 19;17(10):e94926. doi: 10.7759/cureus.94926. PMID: 41116804; PMCID: PMC12535773.
** Weight regain after cessation of medication for weight management: systematic review and meta-analysis. BMJ 2026; 392 doi: https://doi.org/10.1136/bmj-2025-085304 (Published 07 January 2026)
Photo courtesy of World Obesity Federation