LP-1 analogues and related incretin-based medicines have, within just a few years, significantly changed the medical treatment of overweight and obesity.
Clinical trials demonstrate weight loss of 15–20% of body weight during active treatment. However, both clinical experience and real-world data show that many patients discontinue treatment – often within the first year. The key question is therefore not only whether weight loss medication works, but what happens when treatment stops.
Based on a comprehensive systematic review and meta-analysis published in The BMJ (2026), new evidence shows that both weight loss and cardiometabolic improvements are largely reversible, and that weight regain after stopping medication occurs faster than after behavioural weight management programmes (BWMP). This development cannot be explained solely by the size of the initial weight loss, but suggests that pharmacological treatment alone does not establish lasting behavioural and self-regulation skills.
NICE has documented that GLP-1 “cannot stand alone” and recommends that weight loss medication should not be used as monotherapy, but only as part of a structured weight management programme. Research shows that Total Diet Replacement (TDR) over 8–12 weeks can achieve weight loss comparable to weight loss medication without risk of malnutrition, and is used within NHS weight management programmes.
Why is this knowledge important?
Overweight and obesity are chronic, relapsing conditions characterised by biological counter-regulation of weight loss. Regardless of treatment type, compensatory mechanisms are activated during weight loss, including increased appetite, reduced energy expenditure, and altered hormonal signalling.
Weight loss medication reduces hunger and increases satiety through both central and peripheral mechanisms. The effect during active treatment is well documented, but there has been a lack of comprehensive quantitative assessment of what happens after treatment discontinuation. Previous research has primarily focused on the magnitude of weight loss – not on weight maintenance and metabolic progression after stopping medication.
The purpose of the BMJ study
- Quantify the rate and extent of weight regain after stopping weight loss medication
- Examine changes in cardiometabolic markers after discontinuation
- Compare weight regain after medical treatment with behavioural weight management programmes
- Support more realistic and evidence-based clinical counselling
Data basis and study design
The review included 37 studies (63 intervention arms) comprising 9,341 adults with overweight or obesity. The studies included both older medications (e.g. orlistat and sibutramine) and newer, more potent incretin mimetics such as semaglutide and tirzepatide. Participants received at least 8 weeks of treatment and had a minimum of 4 weeks’ follow-up after treatment discontinuation.
The primary outcome was the rate of weight regain after stopping treatment. Secondary outcomes included HbA1c, fasting glucose, blood pressure and lipid profile. The use of multiple statistical models strengthens the validity of the results.
Rate and extent of weight regain and metabolic markers
After stopping weight loss medication, significant and relatively rapid weight regain is observed:
- This suggests that medication may need to be taken long-term or lifelong
- Average weight regain is approximately 0.4 kg per month, corresponding to 4–5 kg within the first year
- Body weight is estimated to return to baseline after approximately 1.7 years
- With newer and more potent incretin mimetics (semaglutide and tirzepatide), weight regain is faster – up to 0.8 kg per month – with return to baseline weight after around 1.5 years
- Improvements in HbA1c, fasting glucose, blood pressure and lipid profile decline after discontinuation and are projected to return towards baseline within approximately 1.4 years
- Weight regain occurs faster after stopping medication than after behavioural weight management programmes (BWMP)
In clinical trials, participants regain, on average, all the weight they lost within approximately 18 months after stopping medication. This is almost four times faster than the weight regain typically seen after completing diet- and activity-based weight management programmes. At the same time, achieved health improvements disappear, and blood pressure, cholesterol and blood glucose return towards baseline.
Overall, the results indicate that weight loss medication must be used long-term or lifelong to maintain its effect.
Evidence-based findings and treatment perspectives
In 2023, approximately 117,500 Danish adults redeemed prescriptions for weight loss medication, corresponding to around 2.4% of the adult population. In Europe, the price is typically around €300 per month without public reimbursement, depending on dose and product.
The overall evidence documents that weight loss medication – including GLP-1 receptor agonists – is highly effective at inducing weight loss during active treatment, but that both weight and cardiometabolic improvements are largely reversible after discontinuation. Weight regain occurs faster than after behavioural weight management programmes and cannot be explained solely by the magnitude of initial weight loss.
This underscores that pharmacological treatment reduces biological barriers to weight loss but does not in itself establish the behavioural and self-regulatory skills necessary for long-term weight maintenance.
NICE explicitly recommends that GLP-1 receptor agonists should not be used as monotherapy, but only as part of a structured weight management programme. The NHS offers weight loss medication to patients with a BMI over 40 and relevant comorbidities, based on assumptions of approximately two years of treatment and gradual weight regain after discontinuation. However, new data show that more than 50% discontinue treatment within one year, and that weight loss is, on average, regained within approximately 18 months – significantly altering the health-economic assumptions.
At the same time, evidence shows that Total Diet Replacement programmes of 8–12 weeks can achieve weight loss comparable to medication while preventing malnutrition. These programmes are significantly less expensive and already integrated into structured weight management pathways, making them a more cost-effective and scalable solution within the NHS framework.
Within this treatment paradigm, the clinical dietitian plays a key role. Through individualised nutrition therapy, structured meal planning, and work on behaviour and self-regulation, medically induced weight loss can be translated into weight stability and sustainable lifestyle changes.
The evidence clearly indicates that weight loss medication must be taken long-term or lifelong if weight is to be maintained, and that GLP-1 receptor agonists should be used as an integrated tool within long-term, multidisciplinary treatment – not as an isolated intervention – because weight loss medication “cannot stand alone”.
Sources
- The BMJ. Weight regain and cardiometabolic changes after stopping weight-loss medication: a systematic review and meta-analysis. BMJ. 2025.
- Dobbie LJ, Parretti HM, Fallows E, Le Brocq S, et al. Ten Top Tips for the Management of GLP-1 Receptor Agonists in Adults within Primary Care. Obesity Facts. 2025.
- Møller FS, Hegelund ER. Who uses weight loss medicines in Denmark? Statistics Denmark.
