Quick clinical answer
Withdrawal studies show that substantial weight regain can follow discontinuation of semaglutide or tirzepatide. These findings support planning ongoing care; they do not prove that every patient needs the same medicine indefinitely. Decisions require an individual assessment of benefit, adverse effects, clinical indications, preferences and access. The World Health Organization’s recommendation for long-term GLP-1 treatment in adults with obesity is conditional, reflecting remaining uncertainties and practical limitations.[1]
What do the withdrawal studies actually show?
Three studies are particularly useful for professional discussion. Their designs matter as much as their headline results.
STEP 1 extension: An exploratory follow-up included 327 participants from the original semaglutide trial. Both study treatment and structured lifestyle intervention stopped after 68 weeks. One year later, participants previously receiving semaglutide had regained, on average, about two-thirds of their earlier weight loss. Several cardiometabolic improvements moved back towards baseline. This was a selected extension group, and stopping both interventions complicates attribution to medication withdrawal alone.[2]
STEP 4: After a 20-week semaglutide run-in, 803 participants were randomised to continue treatment or switch to placebo. Both groups continued lifestyle intervention. Over the following 48 weeks, the continuation group lost a further 7.9% of body weight on average; the placebo group gained 6.9%. These changes were measured from randomisation, not the original study baseline. Participants had successfully reached the trial’s maintenance dose before randomisation.[3]
SURMOUNT-4: Following 36 weeks of tirzepatide treatment, 670 participants were randomised to continue treatment or switch to placebo. Over the next 52 weeks, the placebo group gained an average 14.0% from its week-36 weight, while the continuation group lost a further 5.5%. The trial excluded diabetes, enrolled people who completed the initial treatment period, and did not test flexible dose reductions after randomisation.[4]
Together, these studies support anticipating recurrence after withdrawal. They are not trials of every possible maintenance strategy, every population or an individual patient’s eventual outcome.
Maintenance is more than a target weight
A stable weight can coexist with continuing clinical benefit. Conversely, a lower weight does not automatically establish that treatment is suitable or well tolerated.
WHO frames obesity as a chronic disease requiring comprehensive care, including attention to complications and supportive behavioural interventions. Its guidance does not make medication the whole care plan.[1] NICE’s UK guidance similarly recommends reviewing medicine effects, reinforcing behavioural support and providing maintenance support when medicines stop. These are international recommendations; they do not replace South African prescribing requirements.[5]
For clinical teaching, MedBase proposes four questions to structure a maintenance review:
- What benefit are we trying to maintain? Record the person’s priorities and relevant health outcomes, rather than assuming continued weight loss is always the goal.
- What has changed? Revisit tolerability, eating patterns, activity, other medicines, practical access and the person’s willingness to continue.
- What needs reassessment? Decide which measurements and investigations would change management in this individual.
- What happens next? Agree the review plan, responsibilities and reasons to make contact sooner.
These are discussion prompts, not a validated assessment tool or a substitute for condition-specific guidance.
If treatment changes, make the follow-up plan explicit
Stopping may arise from adverse effects, a change in clinical circumstances, affordability or a person’s informed preference. The response should be a clinical conversation with a documented plan.
The cited withdrawal trials do not establish a universal taper, intermittent schedule or replacement regimen. Nor should their results be used to promise that a particular diet, supplement or alternative peptide will prevent regain. The relevant question is which options have evidence, a suitable indication and a reasonable balance of benefit and burden for this person.
Continuity matters even when medication stops. Agree how progress will be reviewed and how the person can re-enter care if difficulties emerge. NICE explicitly recommends support for people stopping weight-management medicines.[5] The clinician should distinguish a planned treatment change from a person becoming lost to follow-up.
Keep product quality and local requirements in view
Evidence for a studied medicine cannot be transferred automatically to every product advertised under the same ingredient name. SAHPRA warns about unregistered peptide products sold through informal channels and the risks of products whose quality, safety and effectiveness have not been established.[6]
South African practitioners should check the current registration, approved product information and applicable requirements for the exact product being considered. This article does not determine any individual product’s current registration status or provide prescribing instructions.
Connecting evidence with professional education
MedBase is a doctor-led Medical Aesthetics and Anti-Ageing Academy in Waterkloof, Pretoria, serving registered healthcare practitioners. Its educational interests include medical weight management, peptide medicine and aesthetic medicine.
Dr Luhard Jansen van Vuuren is MedBase’s co-founder and clinical mentor. A useful educational focus is connecting evidence appraisal with patient selection, realistic expectations and follow-up. This article complements MedBase’s October discussion of muscle preservation during medical weight loss and its September discussion of integrated clinical care.
Practitioners can explore the current training programme, review the planned 2027 education areas and register their interests through the practitioner portal. MedBase provides professional education; this page is not a patient consultation or medicine-ordering service.
Common questions
Does everyone regain all their weight after stopping?
No. The trials report group averages with variation between individuals. They demonstrate substantial average regain, not an inevitable identical outcome for every person.[2] [3] [4]
Does maintenance always mean lifelong use of one medicine?
No. Long-term care and indefinite use of a particular medicine are different decisions. WHO’s recommendation is conditional, and care needs periodic individual reassessment.[1]
Is a tapering protocol established by these trials?
No. The cited withdrawal studies do not establish a universal tapering or intermittent maintenance regimen.[2] [3] [4]
References
- World Health Organization. WHO issues global guideline on the use of GLP-1 medicines in treating obesity. 1 December 2025.
- Wilding JPH et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obesity and Metabolism. 2022;24(8):1553–1564.
- Rubino D et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414–1425.
- Aronne LJ et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024;331(1):38–48.
- National Institute for Health and Care Excellence. Overweight and obesity management, NG246. Medicines and surgery: recommendations 1.17.5–1.17.7. UK guidance.
- South African Health Products Regulatory Authority. Peptide Products – Public Information. Accessed 1 November 2026.
Published by MedBase Clinical Education. Send a correction or source question.