Stopping a GLP-1: what the withdrawal trials found, and what a maintenance dose actually is

Two trials have measured what happens when you stop. On semaglutide, people who lost 17.3% over 68 weeks regained two-thirds of it in the year after stopping, ending 5.6% below where they started. On tirzepatide, people who lost 20.9% in 36 weeks regained 14% over the next year on placebo while those who continued lost a further 5.5%. Both labels are explicit that these drugs are for maintaining weight reduction long term, which is a different claim from finishing a course. A maintenance dose is simply the dose you stay on; the labels do not define a lower one.

9 min read · published Sep 3

The short version

  • 1Semaglutide, STEP 1 extension: 17.3% lost in 68 weeks; two-thirds regained one year after stopping; net 5.6% below baseline at week 120.
  • 2Tirzepatide, SURMOUNT-4: 20.9% lost in 36 weeks; then +14.0% on placebo vs a further 5.5% lost on continued drug over 52 weeks.
  • 389.5% of people who continued tirzepatide kept at least 80% of their loss; 16.6% of those who stopped did.
  • 4Both labels describe the drugs as maintaining weight reduction long term. Neither defines a lower maintenance dose.
  • 5The cost of maintenance is the cost of the drug, indefinitely, which is why the price per month matters more than the price per course.

The question under this one is whether these drugs are a course or a condition. A course ends and the result stays. A condition is managed for as long as you manage it. The two withdrawal trials answer that with numbers, the labels answer it with a word, and the answer is the same from both: this is the second kind.

What happened when people stopped semaglutide

STEP 1 was the trial that made Wegovy famous. Its extension followed a subset of participants for a further year after everything stopped, the drug and the lifestyle programme both.1 The numbers:

Semaglutide 2.4 mg, STEP 1 extension
Lost on the drug, weeks 0 to 6817.3% of body weight
Regained in the year after stopping11.6 points
Net position at week 120, a year off the drug5.6% below the start
Share of the loss given backtwo-thirds

One year after withdrawal of once-weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two-thirds of their prior weight loss, with similar changes in cardiometabolic variables. Findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health.

Wilding et al., STEP 1 extension, conclusions

The phrase to hold onto is "similar changes in cardiometabolic variables". Blood pressure, lipids and blood sugar improved on the drug and went back with the weight. The regain is not cosmetic.

What happened when people stopped tirzepatide

SURMOUNT-4 was built to answer this question directly. Everyone took tirzepatide for 36 weeks, then half were switched to placebo without being told and half continued, for another year.2

Tirzepatide, SURMOUNT-4ContinuedSwitched to placebo
Lost in the 36-week lead-in (everyone)20.9%
Change over the next 52 weeksa further −5.5%+14.0%
Kept at least 80% of the loss at week 8889.5% of people16.6%

Two things in that table. The people who stopped gave back 14 of the 20.9 points in a year, the same two-thirds pattern as semaglutide. And the people who continued did not merely hold; they lost a further 5.5%, which is the "maintained and augmented" in the authors' conclusion.2 Continuing past the point where you feel done is not maintenance in the sense of standing still. It is more loss, more slowly.

What the labels say the drugs are for

Both labels use the same phrase, and it is the answer to the course-or-condition question in the manufacturers' own words. Zepbound is "to reduce excess body weight and maintain weight reduction long term".3 Wegovy is "to reduce excess body weight and maintain weight reduction long term".4 Not to reach a target. To maintain, long term. The regulators approved these as ongoing treatments, and the trials above are why.

What a maintenance dose actually is

People searching for a maintenance dose usually mean a lower dose you drop to once you have reached goal, and the honest answer is that the labels do not define one for the injections. The maintenance dose is whichever dose you climbed to and stay on: 5 to 15 mg for Zepbound, 1.7 or 2.4 mg for the Wegovy pen, with the only explicitly named maintenance dose being the Wegovy tablet's 25 mg.4 Zepbound's label names its starting dose and says it is not a maintenance dose;3 it does not name a step-down.

That does not mean nobody steps down. Prescribers do reduce doses, stretch intervals, or move people to a lower rung once weight is stable, and there is a real logic to it: a lower dose costs less and has fewer gut effects. But it is clinical judgement rather than a labelled regimen, and the trial that comes closest, SURMOUNT-4, tested full dose against nothing, not full dose against half. What the evidence supports is that some dose, continued, holds the weight. What it does not yet tell you is how low that dose can go.

If it seems to have stopped working

The plateau is the point in every trial where the curve flattens, usually somewhere past a year, and it is not the drug failing; it is the drug having done what it does at that dose. Three things are true at a plateau. The drug is still working, in the sense that stopping it would produce the regain above. A higher rung may produce more, which is what Wegovy's 7.2 mg dose exists for and what the switch to tirzepatide is usually about. And a plateau at 15% or 20% below where you started is, by the standard of every prior treatment for obesity, the result.

The cost of the second kind of drug

If it is a condition rather than a course, the price that matters is the price per month, indefinitely, and not the price of getting to goal. That reframes every number on this site. A year at maintenance:

Route at a maintenance dosePer monthPer year
Compounded semaglutide, cheapest on our boardfrom $69from about $830
Compounded tirzepatide, cheapest on our boardfrom $119from about $1,430
Wegovy tablet, 25 mg, direct$299$3,588
Wegovy pen, 2.4 mg, direct$349$4,188
Zepbound, 10 to 15 mg, direct$699$8,388
Either brand, commercial plan that covers it$25$300

The live board, verified on each seller's page today, is where the top two rows come from:

The compounded route's whole case is that row: a price that can be sustained for years, at the cost of FDA review of the product. Is compounded semaglutide safe sets out that trade in FDA's own words.

The honest summary

Stopping gives back about two-thirds of the loss within a year, on either molecule, with the health improvements going back alongside it. Continuing holds it and, on tirzepatide, adds to it. The labels call the drugs long-term maintenance treatments and do not define a step-down dose, though prescribers use one in practice. So the decision at goal weight is not whether to stop. It is which dose, from which seller, at which price, you can stay on for as long as it takes, and that is a monthly number.

Sources4
  1. Wilding et al., Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension, Diabetes Obes Metab 2022 read Sep 3From week 0 to week 68, mean weight loss was 17.3% (SD: 9.3%) with semaglutide and 2.0% (SD: 6.1%) with placebo. Following treatment withdrawal, semaglutide and placebo participants regained 11.6 (SD: 7.7) and 1.9 (SD: 4.8) percentage points of lost weight, respectively, by week 120, resulting in net losses of 5.6% (SD: 8.9%) and 0.1% (SD: 5.8%), respectively, from week 0 to week 120. ... One year after withdrawal of once-weekly subcutaneous semaglutide 2.4 mg and lifestyle intervention, participants regained two-thirds of their prior weight loss, with similar changes in cardiometabolic variables. Findings confirm the chronicity of obesity and suggest ongoing treatment is required to maintain improvements in weight and health.
  2. Aronne et al., SURMOUNT-4, tirzepatide randomised withdrawal, JAMA 2024 read Sep 3Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. ... Participants ... who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo ... withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction.
  3. Zepbound prescribing information (DailyMed), indication and dosing read Sep 3to reduce excess body weight and maintain weight reduction long term in adults with obesity or adults with overweight in the presence of at least one weight-related comorbid condition. ... The recommended starting dosage of ZEPBOUND for all indications is 2.5 mg injected subcutaneously once weekly for 4 weeks.
  4. Wegovy prescribing information (DailyMed), indication and tablet maintenance dose read Sep 3to reduce excess body weight and maintain weight reduction long term in adults with obesity, or in adults with overweight in the presence of at least one weight-related comorbid condition. ... The recommended maintenance dosage of WEGOVY tablets is 25 mg orally once daily for cardiovascular risk reduction and weight reduction in adults.

Common questions

What happens when you stop taking a GLP-1?

The weight comes back, most of it within a year. In the STEP 1 extension, people who lost 17.3% on semaglutide regained two-thirds of it in the year after stopping. In SURMOUNT-4, people who lost 20.9% on tirzepatide regained 14 points over the following year on placebo, while those who continued lost a further 5.5%. Blood pressure, lipids and blood sugar returned with the weight.

Do you have to take GLP-1s forever?

Both labels describe the drugs as treatments to reduce weight and maintain the reduction long term, and the withdrawal trials show why: stopping returns about two-thirds of the loss within a year. Whether that means forever is a decision between you and a prescriber, but the evidence treats obesity as a condition managed for as long as it is treated, not a course that is completed.

What is the maintenance dose of Wegovy or Zepbound?

The dose you climbed to and stay on. For the Wegovy pen that is 1.7 or 2.4 mg; for Zepbound, 5 to 15 mg; the Wegovy tablet's label names 25 mg as its maintenance dose. Neither injection's label defines a lower step-down dose. Prescribers do reduce doses in practice once weight is stable, but that is clinical judgement rather than a labelled regimen.

Why has my GLP-1 stopped working?

Usually it has not. Every trial curve flattens past about a year; that plateau is the drug's full effect at that dose, not a failure. Stopping at a plateau still produces the regain seen in the withdrawal trials. If more loss is the goal, the options are a higher dose, such as Wegovy 7.2 mg, or a switch to tirzepatide, which lost 20.2% against semaglutide's 13.7% head-to-head.

How much does it cost to stay on a GLP-1 long term?

The monthly price, indefinitely. At maintenance doses that is from about $830 a year for compounded semaglutide and $1,430 for compounded tirzepatide on our board, $3,588 for the Wegovy tablet and $4,188 for the pen direct from Novo, $8,388 for Zepbound at 10 mg and above direct from Lilly, or about $300 a year with a commercial plan that covers either brand at a $25 copay.

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