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Stopping question · 3 trials · 7 labels
Weight comes back when you stop. In the two trials that took away only the drug, people gained 6.9% and 14.0% of their body weight back within a year. In the one trial that ended the drug and the diet program together, two-thirds of the lost weight had returned.
Source: Trials and labels read 2026-08-13
All three studies followed people who had already lost weight on a GLP-1 drug. Some stopped the drug and others continued. The important difference is whether the diet and activity program stopped too.
NCT03548935
327 people · 52 weeks
One year after everything stopped, about two-thirds of the weight lost had come back. The blood-pressure and blood-sugar improvements had moved back toward where they began.
After stopping the drug
regained 11.6 of the 17.3 points lost, ending 5.6% below where they started
For people who continued
This study did not include a group that continued treatment.
NCT03548987
803 people · 48 weeks
Everyone had already lost about a tenth of their body weight in the 20-week run-in. Swapping the drug for a dummy injection turned that into a gain, while staying on it kept the weight coming off.
After stopping the drug
gained 6.9%
For people who continued
lost a further 7.9%
NCT04660643
670 people · 52 weeks
This is the widest gap of the three. The lead-in took a mean 20.9% off over 36 weeks. The group moved to a dummy injection then gained 14.0% back over the next year. The group that stayed on the drug lost another 5.5%.
After stopping the drug
gained 14.0%
For people who continued
lost a further 5.5%
STEP 4 and SURMOUNT-4 removed only the drug. The diet program, study visits and weekly injection routine continued. STEP 1 ended the drug and the support program together, which is closer to what many people mean when they say they stopped treatment.
STEP 4 and SURMOUNT-4
STEP 1 extension
Why STEP 1 needs extra caution
The tirzepatide label prints a second table for the same trial, and almost nobody quotes it. Over the year after the switch, these are the mean changes for the group taken off the drug and the group kept on it.
| Measure | Taken off the drug | Kept on it |
|---|---|---|
| Waist | +7.8 cm | −4.3 cm |
| Upper blood-pressure number | +8.2 mmHg | +2.0 mmHg |
The semaglutide extension reports the same direction in its own words. The improvements seen over the year on the drug moved back toward the starting point, for most of what it measured.
None of the labels checked gives a step-down schedule. They do give a rule for a dose that was missed, and the rules are not the same. 7 current labels were read, and 2 of them tell you to go back down the ladder after a longer gap. The rest say nothing about it at all.
| Product | Schedule | A missed dose can still be taken | Coming back after a longer gap |
|---|---|---|---|
| Wegovysemaglutide | once weekly | More than 2 days before the next one“If one dose of WEGOVY injection is missed and the next scheduled dose is: more than 2 days away, administer WEGOVY injection as soon as possible. less than 2 days away, do not administer the WEGOVY injection dose.” | “If 2 or more consecutive doses of WEGOVY injection are missed, reinitiate dosage escalation at a lower dosage to reduce the risk of gastrointestinal adverse reactions” |
| Ozempicsemaglutide | once weekly | Within 5 days“If a dose is missed, administer OZEMPIC as soon as possible within 5 days after the missed dose. If more than 5 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day.” | The label does not say |
| Zepboundtirzepatide | once weekly | Within 4 days“If a dose is missed, instruct patients to administer ZEPBOUND as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day.” | The label does not say |
| Mounjarotirzepatide | once weekly | Within 4 days“If a dose is missed, instruct patients to administer MOUNJARO as soon as possible within 4 days (96 hours) after the missed dose. If more than 4 days have passed, skip the missed dose and administer the next dose on the regularly scheduled day.” | The label does not say |
| Trulicitydulaglutide | once weekly | At least 3 days before the next one“If a dose is missed, instruct patients to administer the dose as soon as possible if there are at least 3 days (72 hours) until the next scheduled dose. If less than 3 days remain before the next scheduled dose, skip the missed dose and administer the next dose on the regularly scheduled day.” | The label does not say |
| Saxendaliraglutide | once daily | No catching up — the next dose is the next one due“If a dose is missed, resume the once-daily regimen as prescribed with the next scheduled dose. Do not administer an extra dose or increase the dose to make up for the missed dose.” | “If more than 3 days have elapsed since the last SAXENDA dosage, reinitiate SAXENDA at 0.6 mg daily and follow the dosage escalation schedule in Table 1, to reduce the risk of gastrointestinal adverse reactions associated with reinitiation of treatment.” |
| Rybelsus and Ozempic tabletssemaglutide | once daily | No catching up — the next dose is tomorrow’s“If a dose is missed, skip the missed dose and take the next dose the following day.” | The label does not say |
The spread is the finding. Four days on tirzepatide, five on Ozempic, three on Trulicity, two days of warning on Wegovy. On the daily products there is no catching up at all. A rule read off one carton does not transfer to the next one.
Both randomized withdrawal trials sit in the FDA-approved labeling of the drug they tested. They are in the same clinical studies section that carries the weight-loss figure everybody quotes. The Wegovy labeling calls it Study 5, the Zepbound labeling calls it Study 4, and each prints the table with the gain in it.
The Wegovy labeling also states the limit of its own trial, which is rarer and more useful than anything a summary of it will tell you:
Because patients who discontinued WEGOVY injection during titration and those who did not reach the 2.4 mg weekly dose were not eligible for the randomized-treatment period, the results may not reflect the experience of patients in the general population who are first starting WEGOVY injection.
Read plainly: everyone in that trial had already climbed to the full dose and stayed there for months. Somebody who stops in week six is not in the number.
This is the part people underestimate, and every label states it outright. Nothing switches off on the day of a missed injection.
| Drug | Half-life | What the label says about after the last dose |
|---|---|---|
| Semaglutide (Wegovy) | about 1 week | “With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for about 5 to 7 weeks after the last injectable dose of 2.4 mg or 7.2 mg or oral dose of 25 mg.” |
| Semaglutide (Ozempic) | about 1 week | “With an elimination half-life of approximately 1 week, semaglutide will be present in the circulation for about 5 weeks after the last dose.” |
| Tirzepatide (Zepbound) | about 5 to 6 days | The label gives the half-life and no clearance window |
| Liraglutide (Saxenda) | about 13 hours | The label gives the half-life and no clearance window |
The labels do name reasons to stop, and one of them turns on how long the drug lingers rather than on how it is working. The Wegovy labeling tells prescribers to stop it at least two months before a planned pregnancy:
discontinue WEGOVY at least 2 months before a planned pregnancy because of the long half-life of semaglutide
The three trials answer one shape of question and leave the ones beside them open. These are the gaps, and each is a study nobody has run rather than an answer of no.
The trials report where people were a year later rather than the shape of the climb. Both labels print a chart of it: Figure 8 in the Wegovy labeling, Figure 6 in the Zepbound one. A rate of regain per month is not a figure either trial states.
That is a different question with a different source. See what people report when the effect fades — and for the reactions themselves, how long they last has no published answer.
The last evidence gap is the largest. 11 of the 36 compounds tracked here have no human safety record at all. For those there is no trial to stop and nobody to weigh afterward, which is set out on each record and on the page about combining them.
The findings below come directly from the published studies. Whether to come off one of these drugs, and how, belongs to the person who prescribes it. They can see the rest of the picture, and none of these trials was run on you.