The two trials
The STEP 1 trial extension followed participants for a year after once-weekly semaglutide 2.4 mg and the accompanying lifestyle programme were withdrawn. One year on, participants had regained roughly two-thirds of the weight they had lost. Cardiometabolic markers that had improved during treatment moved back toward where they started.
SURMOUNT-4 tested the same question for tirzepatide, and it was designed to isolate the drug specifically. Everyone took tirzepatide for 36 weeks, and only then were participants randomly assigned to continue or switch to placebo. From week 36 to week 88, the continuation group lost a further 5.5% of body weight. The placebo group regained 14.0%. By week 88 the two groups had ended up at −25.3% and −9.9% from baseline respectively.
The trials used different drugs, different designs and different populations, and they point the same way. Weight regain after withdrawal is the expected outcome, not the unlucky one.
Why this is not a failure of willpower
It is tempting to read regain as people going back to old habits once the drug stops working. The physiology is less flattering to that reading. GLP-1 receptor agonists work in large part by changing appetite signalling — how hungry you feel, how quickly you feel full, how loud food is as a thought. Remove the drug and that signalling returns to roughly where it was.
The body also defends against weight loss regardless of how the loss was achieved, through changes in appetite hormones and energy expenditure that persist well after the loss itself. This is well documented in people who lose weight by any means, and it is a large part of why maintenance is harder than loss.
Framed that way, the trial results are not surprising at all. A drug that suppresses appetite while you take it suppresses appetite while you take it.
What this means for the decision in front of you
It means treating a GLP-1 as an ongoing treatment rather than a course, in the same way blood pressure medication is ongoing. That reframing has consequences that are financial as much as clinical, and the financial ones are the reason so few sales pages raise it.
Run the arithmetic over the horizon you would actually be treating for, not over the introductory month. A programme at a promotional rate for three months and a standard rate thereafter is, for planning purposes, the standard rate. If that number does not work over two years, it does not work, and finding that out in month four is expensive.
It also means the exit terms matter more than they look. If cost, side effects or supply force a stop, the trial evidence says what follows. Knowing the cancellation policy before you start is part of taking the treatment seriously, not a sign of doubt about it.
Questions worth putting to a prescriber
None of this is a reason not to take a GLP-1, and it is not our place to tell you either way. It is a set of things to have settled before you begin, with someone qualified to answer them for your situation:
- What is the plan if I need to stop — for cost, for side effects, or because supply changes?
- Is there a maintenance dose you would move me to, and what does that cost?
- What happens to the conditions I am treating alongside weight if the weight returns?
- How will we decide whether this is working, and by when?
- If I stop, what support is there for the period afterwards?
What the evidence does not say
It does not say regain is universal or complete. Both trials report means, and means conceal wide individual variation — some participants maintained a substantial part of their loss. Observational work since has found a meaningful minority holding most of it a year out.
It does not say the treatment period was wasted. Time spent at a lower weight has its own effects on blood pressure, glycaemic control and joint load, and those are real while they last.
And it does not tell you what will happen to you. It tells you what happened on average to large groups of people in controlled conditions, which is the best available guide and still not a prediction. Take it to a prescriber who knows your history and let them apply it.