The question that arrives late in the appointment
It is rarely the first question. It comes near the end, after the practical matters, usually phrased as a hypothetical even when it is not one. What happens if I stop.
Weight returns after this class of medicine stops, and that part has not been in dispute for years. How much returns is disputed, and the two most credible answers differ by a wide margin. Anyone quoting a single figure as the answer has read one of them.
Prescription framing first, because it decides who this is for. In Malaysia these medicines are Group B poisons under the Poisons Act 1952, supplied only by a registered medical practitioner or a registered pharmacist against a valid prescription. What a doctor checks before prescribing them is the front half of the subject. This is the back half.
What the withdrawal trials found
The trial that started the conversation followed 333 people after the medicine was withdrawn, 232 who had been taking it and 101 on placebo, and analysed 327 of them. Over 68 weeks of treatment, mean weight loss had been 17.3% against 2.0%. In the year after withdrawal the treated group regained a mean of 11.6 percentage points of body weight, against 1.9 on placebo. From the start of the study to week 120, net weight loss stood at 5.6% against 0.1%.
The least quoted part of that result is the cardiometabolic one. Improvements in the measured risk factors that had appeared by week 68 reverted towards baseline by week 120 for most variables. The weight came back and the blood work followed.
A second withdrawal trial, in JAMA in December 2023, ran the same design on the dual agonist. After a 36-week lead-in, 670 participants were randomised to continue or switch to placebo for 52 weeks. Between week 36 and week 88 the continuing group changed by minus 5.5% of body weight. The placebo group changed by plus 14.0%.
Regain is a distribution, and the average hides it
A later analysis of that trial, in JAMA Internal Medicine, went past the mean. It sorted the 308 placebo participants by how much of their lost weight had come back a year after withdrawal. 54 regained less than a quarter. 77 a quarter to a half. 103 half to three quarters. 74 three quarters or more.
Four groups, four experiences of the same medicine stopping, and an average describes none of them. The same analysis found that the more weight came back, the more of the earlier cardiometabolic improvement reversed with it. Regain is a clinical question before a cosmetic one.
The pooled curve, and what it does not say
In March 2026 a systematic review with nonlinear meta-regression in eClinicalMedicine pooled 48 studies, 6 of them randomised, with 3,236 participants in the model. At one year after stopping, 60% of the weight lost had returned. The curve then flattens, with regain estimated to plateau at 75.3% of the weight lost, on a confidence interval of 68.9 to 81.6, and a rate constant corresponding to a half-life of about 23 weeks.
Read the shape rather than the number. Regain is quick at first and decelerates, and the model puts the plateau below where the person started. Worth stating plainly, because the folk version of this medicine ends with people heavier than they began, and nothing supports that. About a quarter of what was lost stays lost. Beyond roughly two years off treatment there is no evidence.
The real-world number that disagrees
A retrospective cohort published in 2026 looked at 7,938 adults across a large American health system who started one of these injectable medicines and stopped within three to twelve months. The group treated for obesity had lost a mean of 8.4% of body weight before stopping. A year later they had regained a mean of 0.5%.
That is not a rounding of the trial figure. Taken alone it suggests the problem barely exists.
It should not be, and the same paper says why. The cohort had lost far less to begin with, 8.4% against 17.3% in the trial, so there was less to give back. In the year after stopping, 19.6% restarted the same medicine and 35.2% received some other obesity treatment, including another medication in 27.4% and bariatric surgery in 0.6%. More than half did not simply stop, and the authors note they could not see why anyone had discontinued.
Why the two answers do not need reconciling
The trials answer a controlled question: if someone who has lost a large amount on this medicine stops, and nothing replaces it, what happens. The cohort answers a practical one: what happens to people who stop in ordinary care, where stopping is often a change of plan rather than an ending.
Both are honest answers to their own question. Averaging them produces a number that answers neither, and picking the flattering one is how this subject gets misused in both directions, by marketing that implies the loss will hold and by commentary that implies it all comes back.
What the Malaysian guideline already said about rebound weight
None of this is new to the national guidance. The Ministry of Health and Malaysian Endocrine and Metabolic Society guideline on obesity states that obesity is a chronic disease, that pharmacotherapy should be considered long term, that courses of six months or less do not produce sustained weight loss once the medication stops, and that rebound weight gain follows cessation.
It also sets the conditions of use: an adjunct to diet, activity and behavioural change, with face-to-face review monthly for three months and at least three-monthly after. Read next to the withdrawal trials, that schedule looks less like administration and more like the mechanism by which the maintenance question keeps being asked, built into how the pathway here is structured.
The question to settle before the first dose
The useful conversation about stopping happens before starting, and it is one question: what is the plan for afterwards. Long-term treatment, a planned handover to something else, or an accepted partial result. Three defensible answers. Having no answer is the one that reliably disappoints.
Nothing prevents regain outright. No taper, no supplement, no clinic protocol, and anything claiming otherwise describes something that has not been shown. What the evidence supports is narrower: the plateau sits below the starting weight, the trajectory is predictable, and its size depends heavily on what replaces the medicine. The assessment that decides whether to start is where that plan gets made.
The skin question runs on its own track, set out in what a large loss does to skin.
A patient who regains weight after stopping has not failed at anything. A chronic condition returned when its treatment stopped, which is what chronic conditions do. Worth saying in a field that files the same event under lapse.
