If you're paying for a GLP-1 every month, "what happens if I stop?" is really a question about the next ten years. The trials give a clear answer for weight: most of it comes back over the following year [1] [3]. They don't say the drug stops being worth taking, and they don't say you can never stop. They show what to plan for. This page covers semaglutide (Ozempic, Wegovy) and tirzepatide (Zepbound, Mounjaro).
Three trials stopped the drug on purpose
Most drug trials compare a drug with placebo from day one. These three did something different: everyone took the drug first, then some people were switched to placebo without knowing it, or the drug was stopped and people were followed. That design isolates the effect of stopping.
| Trial | Drug | Weight lost before the switch | After stopping | Stayed on |
|---|---|---|---|---|
| STEP 1 extension (n=327) [1] | Semaglutide 2.4 mg | 17.3% by week 68 | Regained 11.6 points by week 120 | Not studied (everyone stopped) |
| STEP 4 (n=803) [2] | Semaglutide 2.4 mg | 10.6% in a 20-week run-in | +6.9% from week 20 to 68 | −7.9% from week 20 to 68 |
| SURMOUNT-4 (n=670) [3] | Tirzepatide, 10 or 15 mg | 20.9% in a 36-week lead-in | +14.0% from week 36 to 88 | −5.5% from week 36 to 88 |
Percentages are changes in body weight. STEP 1 extension figures are among people who completed the off-treatment year.
Semaglutide: two-thirds of the loss came back within a year
The STEP 1 extension followed 327 people after the main 68-week trial of semaglutide 2.4 mg, the Wegovy dose, ended. By week 68 they'd lost 17.3% of their weight on average. Then the drug and the trial's lifestyle program stopped. By week 120, they had regained 11.6 percentage points, leaving a net loss of 5.6% [1]. The authors summed it up as people regaining "two-thirds of their prior weight loss."
There's a second way to read the same data. At week 68, 86.4% of the semaglutide group had lost at least 5% of their starting weight. A year after stopping, 48.2% still had [1]. So about half kept a meaningful loss, and about half didn't. The study was funded by Novo Nordisk, which makes Wegovy and Ozempic.
STEP 4 asked the question more directly. All 803 participants took semaglutide 2.4 mg for 20 weeks and lost 10.6% on average. Then they were randomized: those switched to placebo gained 6.9% over the next 48 weeks, while those who stayed on lost another 7.9% [2]. Novo Nordisk funded STEP 4 and helped design, analyze and write it up.
Tirzepatide: a 14% regain in a year on placebo
SURMOUNT-4 gave everyone tirzepatide for 36 weeks, at the highest dose each person tolerated (10 or 15 mg). The 670 people who went on to the randomized part had lost 20.9% on average. Then half were switched to placebo for 52 weeks [3].
From week 36 to week 88, the placebo group regained 14.0% of body weight. The group that stayed on lost another 5.5%. Across the whole 88 weeks, that left the stay-on group 25.3% below where they started and the placebo group 9.9% below [3]. Put another way, 89.5% of people who stayed on kept at least 80% of their earlier loss, against 16.6% of those switched to placebo. Eli Lilly, which makes Zepbound and Mounjaro, sponsored the trial.
Zepbound's label prints this trial's curve. The placebo line climbs steadily from week 36 and is still rising at week 88, the last point measured [4]. The trial ended before anyone could say where the regain would level off.
People who lost more regained more, but still kept more
The STEP 1 extension also looked at who kept the most weight off. People who lost the most during the 68 weeks on semaglutide tended to regain the most weight afterward, yet they still ended week 120 further below their starting weight than people who had lost less [1]. Every analysis in the extension was exploratory, so read them as a pattern, not a promise.
One more detail is easy to miss. In the STEP 1 extension, the trial's structured diet and activity program ended at the same time as the drug. So the regain reflects losing both supports at once, not the drug alone [1]. STEP 4 and SURMOUNT-4 kept lifestyle counseling going for everyone, and their placebo groups still regained, so the regain isn't only about losing the lifestyle support [2] [3].
Blood pressure and other gains faded with the weight
Weight isn't the only thing that moved. In the STEP 1 extension, systolic and diastolic blood pressure rose after the drug stopped and were back at baseline levels by week 120 [1]. The authors reported that, for most measures, the improvements seen during treatment had moved back toward baseline by week 120, a set that included HbA1c (a blood-sugar measure), cholesterol and an inflammation marker.
STEP 4 showed the flip side. Compared with switching to placebo, staying on semaglutide gave a 3.9 mmHg lower systolic blood pressure and a smaller waist by week 68 [2]. For a reader who started a GLP-1 for long-term heart and metabolic health, that's the cost of stopping that doesn't show on the scale.
How long the drug stays in your body after the last dose
Stopping isn't instant, because both drugs last a long time. Semaglutide has a half-life of about one week. Wegovy's label says it "will be present in the circulation for about 5 to 7 weeks after the last" dose [5], and Ozempic's label says "about 5 weeks" [6]. Tirzepatide's half-life is about 5 days on Zepbound's label [4]; that label gives no clearance time, but by the usual five-half-lives rule of thumb it's about a month (our arithmetic). The details are in how long Zepbound stays in your system.
Appetite and side effects after stopping: the trials say little
People often ask whether hunger comes roaring back. None of these trials published an appetite measure for the stopping period that answers that, so there's no trial number to give. The STEP 1 extension didn't systematically collect side effects after the drug stopped [1]. What the trials do show is that weight returned steadily over months, not overnight.
The stomach side effects are tied to taking the drug. Zepbound's label says most nausea, vomiting and diarrhea came while the dose was rising and eased over time [4]. In STEP 4, digestive side effects were reported by 49.1% of people who stayed on semaglutide against 26.1% after the switch to placebo [2]. For changes in the face and skin with weight loss, see Ozempic face.
If you're thinking about stopping, bring these to your prescriber
None of the four labels sets a taper or a stopping schedule, and this page doesn't offer one. A plan to stop, pause or step down is one to make with your prescriber. Three questions make that conversation more useful:
- Is it the cost? Prices vary widely by route and dose. See Zepbound cost and Wegovy cost before deciding cost alone forces a stop.
- Is a lower maintenance dose an option? Wegovy's label lists 1.7 mg as well as 2.4 mg as a maintenance dose; see Wegovy dosage. Zepbound's label lists 5, 10 and 15 mg.
- What about low-dose plans? Some programs offer lower "microdose" plans. They haven't been tested in trials like these; see microdosing GLP-1s and microdose tirzepatide for what's known.
If you have type 2 diabetes, stopping also affects blood sugar, which is why the decision belongs with whoever manages your diabetes. For how the two molecules compare overall, see semaglutide vs tirzepatide, the semaglutide guide and the tirzepatide guide.
Weighing programs on price? The brand Wegovy and Zepbound self-pay programs lineup sets 21 of them side by side, each with its true monthly cost.