What Happens If I Stop Taking Zepbound? What the Trials Show
In the SURMOUNT-4 withdrawal trial, people who stopped tirzepatide regained an average of 14.0% of body weight in 52 weeks, while those who continued lost another 5.5%. Only 16.6% of stoppers kept most of their loss.
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Yes — in the randomized withdrawal trial that tested this directly, most people who stopped tirzepatide (Zepbound) regained a large share of the weight they had lost. In SURMOUNT-4, participants who switched from tirzepatide to placebo after 36 weeks of treatment regained an average of 14.0% of their body weight over the next 52 weeks, while those who kept taking the drug lost another 5.5% [1]. Only 16.6% of the people who stopped kept at least 80% of their original weight loss, compared with 89.5% of those who continued [1]. A second trial, SURMOUNT-MAINTAIN, reached a similar conclusion: long-term treatment is often needed to keep weight down, and lowering the dose to 5 mg may be an alternative to stopping altogether [2]. SURMOUNT-MAINTAIN was funded by Eli Lilly, the maker of Zepbound [2], and the SURMOUNT-4 author list included Lilly employees, with several other investigators disclosing Lilly research support or fees [1]. Some figures below come from a Lilly press release rather than the peer-reviewed papers [4].
What did SURMOUNT-4 find when people stopped tirzepatide?
SURMOUNT-4 was a phase 3 randomized withdrawal trial run at 70 sites in 4 countries [1]. It enrolled adults with a body mass index of 30 or higher, or 27 or higher with a weight-related complication; people with diabetes were excluded [1]. A total of 783 participants entered a 36-week open-label lead-in, receiving once-weekly injections of tirzepatide at a maximum tolerated dose of 10 or 15 mg [1]. During that lead-in, the group lost an average of 20.9% of their starting weight [1].
At week 36, the 670 participants who made it to randomization were split 1:1 into two groups: 335 continued on tirzepatide and 335 switched to placebo, both for 52 weeks under double-blind conditions [1]. The published report lists this cohort’s characteristics as a mean age of 48, 473 (71%) women, and a mean weight of 107.3 kg, without specifying the exact week at which that weight was measured [1].
The results over that year:
| Measure (week 36 to week 88) | Continued tirzepatide | Switched to placebo |
|---|---|---|
| Mean weight change | -5.5% | +14.0% |
| Difference between groups | -19.4 percentage points (95% CI -21.2 to -17.7), P<.001 | — |
| Kept ≥80% of lead-in weight loss | 300 participants (89.5%) | 16.6% |
| Total weight change, week 0 to 88 | -25.3% | -9.9% |
All figures from the published trial report [1]. The trial’s conclusion: withdrawing tirzepatide led to substantial regain of lost weight, while continued treatment maintained and added to the initial reduction [1]. The trial ended at week 88, so there is no data in this study on what happened after that point [1]. The most common side effects in both groups were mild-to-moderate gastrointestinal events, which occurred more often with tirzepatide [1]. The trial is registered as NCT04660643 [1].
How fast does the weight come back after stopping?
Across the whole class of weight-management medications, a BMJ systematic review and meta-analysis put the average regain at 0.4 kg per month after stopping (95% CI 0.3 to 0.5), or 0.3 kg per month versus control when looking only at randomized trials [5]. The review pooled 37 studies with 63 intervention arms and 9,341 participants, searched through February 2025 [5].
The same analysis projected that all cardiometabolic markers would return to their pre-treatment baseline within 1.4 years of stopping [5]. Regain after a medication was faster than regain after a behavioral weight-management program, by 0.3 kg per month (95% CI 0.22 to 0.34), and that speed was independent of how much weight the person had initially lost [5]. In other words, the analysis did not find that bigger losers regain faster [5].
Two limits on those numbers: the average treatment duration in the pooled studies was 39 weeks (range 11 to 176) and average follow-up after stopping was only 32 weeks (range 4 to 104) [5]. For the semaglutide and tirzepatide arms specifically, follow-up data were not available beyond 52 weeks [5]. The review is registered as PROSPERO CRD42024532069 [5].
Does anyone keep the weight off after stopping?
Some do, but they are the minority in the trial data. In SURMOUNT-4, 16.6% of the placebo group still maintained at least 80% of their lead-in weight loss at week 88, compared with 89.5% of the tirzepatide group (P<.001) [1]. Counting from the very start of the study, the group that stopped was still down an average of 9.9% at week 88 [1].
Can you lower the dose instead of quitting?
That is what SURMOUNT-MAINTAIN tested. It was a phase 3b trial across 20 US sites, running 112 weeks total: a 60-week open-label weight-loss period on tirzepatide at a maximum tolerated dose of 10 or 15 mg, followed by a 52-week double-blind maintenance period [2]. Enrollment ran from September 20, 2023 to January 20, 2026, and 441 people took at least one dose during the weight-loss period [2]. Eligible adults had a BMI of 30 or higher, or 27 or higher with at least one weight-related comorbidity, plus at least one self-reported failed dietary attempt [2].
At week 60, those who had lost at least 5% of their weight and tolerated the drug were randomized 3:3:2 — 140 to continue at maximum tolerated dose, 144 to drop to 5 mg, and 94 to placebo, 378 in total [2][4]. At baseline the group had a mean weight of 113.8 kg, BMI 40.1, HbA1c 5.64%, mean age 46.6, 288 (65%) were female, and 67% were White [2]. Of the 378 randomized, 345 (91%) completed the study [2].
The peer-reviewed primary results, measured as percentage weight change from baseline to week 112:
| Group | Week 112 change from baseline | Difference vs placebo |
|---|---|---|
| Continued maximum tolerated dose | -21.9% (95% CI -23.5 to -20.3) | -12.0% (95% CI -13.8 to -10.1) |
| Reduced to 5 mg | -16.6% (95% CI -18.0 to -15.1) | -6.6% (95% CI -8.3 to -5.0) |
| Placebo | -9.9% (95% CI -11.1 to -8.8) | — |
All comparisons were significant at p<0.0001 [2]. These figures come from the trial’s primary estimand — a modified treatment-regimen estimand that assumes no further benefit from assigned treatment once rescue medication starts, and includes everyone randomized [2].
A Lilly press release dated May 12, 2026 reported the same trial using a different analysis (efficacy estimand, mixed-model figures) and absolute weights: the maximum-dose group averaged 112.2 kg at the start, 89.5 kg at week 60, and 88.7 kg at week 112 — essentially no regain — while the 5 mg group went from 113.4 kg to 89.0 kg and then to 94.6 kg, maintaining all but 5.6 kg of their loss on average [4]. The release also framed the primary endpoint as 25.2 kg (22.4%) lost for the maximum-dose group and 19.2 kg (17.0%) for the 5 mg group over the full 112 weeks [4]. Those are company-reported numbers, not the peer-reviewed primary-estimand results [4].
The trial’s own interpretation: continuing at the maximum tolerated dose maintained the weight reduction, and reducing to 5 mg “might provide a valuable alternative to discontinuation, although individuals’ treatment response might vary” [2]. The trial was published in The Lancet [2][3] and presented at the 33rd European Congress on Obesity [4]; a Lancet Department of Error was published June 6, 2026 [2]. It is registered as NCT06047548 [2].
How many people who stopped needed the drug back?
SURMOUNT-MAINTAIN allowed rescue treatment: starting at week 84, 24 weeks after randomization, participants could receive open-label tirzepatide if their regain exceeded 50% of the weight they had lost [2]. This matters for reading the placebo numbers.
Among those who regained at least 50% of their lost weight, rescue tirzepatide was received by 11 of 138 (8%) in the maximum-dose group, 35 of 142 (25%) in the 5 mg group, and 60 of 90 (67%) in the placebo group [2]. So two-thirds of the people who stopped outright and regained enough to qualify ended up back on the drug within the trial [2].
Because rescue was permitted, the placebo arm’s -9.9% at week 112 is not a clean picture of fully untreated regain — many in that arm were taking tirzepatide again by the end [2].
Has a gradual taper been studied?
No. SURMOUNT-MAINTAIN tested one fixed step down — from a maximum tolerated dose of 10 or 15 mg to 5 mg — held for 52 weeks, not a gradual taper schedule [2]. No taper regimen has been trialed and published, so there is no evidence on whether slowly reducing the dose works better than an abrupt change or a single step. The trial authors note that individual treatment response may vary with dose reduction [2]. Any change to a dose is a decision to make with a prescriber.
What happens to blood sugar and diabetes risk after stopping?
SURMOUNT-1 included 2,539 participants with obesity, of whom 1,032 also had prediabetes; they were assigned to tirzepatide 5, 10, or 15 mg or placebo [6]. The prediabetes subgroup was treated for 176 weeks, then followed for a 17-week off-treatment period [6].
During the 176 treatment weeks, the tirzepatide groups lost 12.3% (5 mg), 18.7% (10 mg), or 19.7% (15 mg) of body weight versus 1.3% for placebo (P<0.001) [6]. Type 2 diabetes was diagnosed in 1.3% of tirzepatide participants versus 13.3% of placebo participants over that period (hazard ratio 0.07, 95% CI 0.0 to 0.1, P<0.001) [6].
After 17 weeks off treatment, the gap narrowed but did not close: 2.4% of the tirzepatide group and 13.7% of the placebo group had developed type 2 diabetes (hazard ratio 0.12, 95% CI 0.1 to 0.2, P<0.001) [6]. There is no data beyond 17 weeks off treatment in this analysis [6]. The trial, funded by Eli Lilly, is registered as NCT04184622 [6].
Does switching to a pill preserve the loss?
There is trial evidence for one oral option. ATTAIN-MAINTAIN consisted of two 52-week phase 3b randomized, double-blind, placebo-controlled cohorts in people who had completed the SURMOUNT-5 head-to-head trial and reached a weight plateau [4]. A total of 376 participants were randomized 3:2 to Foundayo (orforglipron) at a maximum tolerated dose of 14.5 mg or 17.2 mg, or to placebo; the trial is registered as NCT06584916 [4].
According to the Lilly press release, participants who switched from a maximum tolerated dose of Wegovy (semaglutide) to Foundayo maintained all but 0.9 kg of their prior weight loss on average after one year, and those who switched from a maximum tolerated dose of Zepbound maintained all but 5.0 kg [4]. Foundayo is a once-daily oral non-peptide GLP-1 receptor agonist that is FDA-approved for chronic weight management; the ATTAIN-MAINTAIN results were published in Nature Medicine [4][10]. These switch figures come from a company press release, not the peer-reviewed primary analysis [4].
Side effects in ATTAIN-MAINTAIN with Foundayo versus placebo included nausea (18.8% vs 4.1%), constipation (13.1% vs 4.1%), vomiting (8.3% vs 3.4%), and diarrhea (7.4% vs 7.5%) [4].
How many people actually stay on Zepbound after a year?
Two real-world datasets give different answers depending on the population. A Prime Therapeutics analysis of commercial claims — an average of 17.9 million members — identified 62,650 adults without diabetes who newly started Wegovy or Zepbound between January 1, 2021 and June 30, 2024; of those, 33,607 (53.6%) met the full study criteria, including continuous enrollment, and made up the analyzed sample [7]. Persistence was defined as no gap longer than 60 days; the mean age was 45.7 and 75.5% were female [7].
| Group | 1-year persistence |
|---|---|
| Tirzepatide (Zepbound), 2023 starters | 64.0% |
| Tirzepatide (Zepbound), first half of 2024 starters | 64.8% |
| Semaglutide (Wegovy), 2021 starters | 33.2% |
| Semaglutide (Wegovy), 2022 starters | 34.1% |
| Semaglutide (Wegovy), 2023 starters | 39.8% |
| Semaglutide (Wegovy), first half of 2024 starters | 58.6% |
Overall 1-year persistence across both drugs rose from 33.2% in 2021 to 60.9% in the first half of 2024; the authors point to shortage resolution, better dose escalation, and better side-effect management as possible reasons [7].
A Military Health System cohort of 10,649 active-duty service members from 2021 to 2025, using a more lenient definition (no gap over 90 days), found higher rates: 1-year persistence of 81.9% for Zepbound, 70.7% for Wegovy, and 34.2% for Saxenda (liraglutide) (log-rank P<.001) [8]. Mean yearly adherence (proportion of days covered) was 78.2% for Zepbound, 71.6% for Wegovy, and 48.7% for Saxenda [8]. In an adjusted Cox model, the hazard of discontinuation was 33% lower for Zepbound than Wegovy (HR 0.67, 95% CI 0.61 to 0.74), and male service members had a higher discontinuation hazard than females (HR 1.12, 95% CI 1.02 to 1.22) [8].
So somewhere between roughly 64% and 82% of people starting Zepbound were still on it a year later, depending on the population and how a lapse was counted [7][8].
What should you discuss with a prescriber before changing anything?
The trial data point in one consistent direction: stopping reverses most of the benefit. Only 16.6% of the SURMOUNT-4 placebo group kept at least 80% of their lead-in loss at week 88 [1]. Continuing at the maximum tolerated dose held weight essentially flat across the maintenance year in SURMOUNT-MAINTAIN [4]. Dropping to 5 mg sat in between — better than stopping, but with about 5.6 kg of average regain, and 25% of those in the 5 mg group who regained at least 50% of their lost weight ended up receiving rescue treatment [2][4].
The SURMOUNT-MAINTAIN authors frame their findings as supporting individualized, patient-centered decisions about ongoing therapy rather than a single rule for everyone [2]. Whether to continue, reduce, switch, or stop is a decision to make with a prescriber, since none of these trials tested a do-it-yourself schedule.
Sources
- PubMed. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial.
- PubMed. Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial.
- The Lancet. Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial.
- Eli Lilly and Company. Lilly’s Foundayo and lower-dose Zepbound helped people maintain weight loss after switching from higher doses of injectable incretin therapy in two late-phase trials. May 12, 2026.
- PubMed. Weight regain after cessation of medication for weight management: systematic review and meta-analysis.
- PubMed. Tirzepatide for Obesity Treatment and Diabetes Prevention.
- PubMed. Trends in 1-year persistence and adherence among initiators of high-potency, weight loss-indicated glucagon-like peptide 1 receptor agonists.
- PubMed. Patterns of Use for GLP-1 Receptor Agonists in a Weight Management Cohort: A Military Health System Database Analysis of Active Duty Service Members From 2021 to 2025.
- PubMed. Time to weight plateau with tirzepatide treatment in the SURMOUNT-1 and SURMOUNT-4 clinical trials.
- PubMed. Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial.
Frequently asked questions
How much weight comes back after quitting Zepbound, and how fast?
In SURMOUNT-4, people who switched from tirzepatide to placebo regained an average of 14.0% of body weight over 52 weeks. Across weight-management medications generally, a BMJ meta-analysis found average regain of 0.4 kg per month after stopping, with cardiometabolic markers projected to return to baseline within 1.4 years.
Does anyone keep the weight off after stopping?
A minority do. In SURMOUNT-4, 16.6% of those who stopped maintained at least 80% of their lead-in weight loss at week 88, versus 89.5% who continued tirzepatide. Counting from the start of the trial, the group that stopped was still down an average of 9.9% at week 88.
Can you lower the Zepbound dose instead of quitting?
SURMOUNT-MAINTAIN tested one fixed step from a maximum tolerated dose of 10 or 15 mg down to 5 mg. At week 112, the 5 mg group was down 16.6% from baseline versus 21.9% for those who continued and 9.9% for placebo. Lilly reported the 5 mg group maintained all but 5.6 kg on average.
Has a gradual taper of Zepbound been studied?
No. SURMOUNT-MAINTAIN tested a single fixed step down to 5 mg held for 52 weeks, not a gradual taper, and no taper regimen has been trialed and published. The trial authors note individual response to dose reduction may vary.
What happens to blood sugar and diabetes risk after stopping?
In SURMOUNT-1's prediabetes subgroup, after 17 weeks off treatment, 2.4% of the tirzepatide group had developed type 2 diabetes versus 13.7% of placebo (HR 0.12, P<0.001). The gap narrowed after stopping but did not close, and no data beyond 17 weeks off treatment has been published from that analysis.
Does switching to a pill preserve the loss?
In ATTAIN-MAINTAIN, participants who switched from Zepbound at a maximum tolerated dose to the oral drug Foundayo (orforglipron) maintained all but 5.0 kg of their prior loss on average after one year, per a Lilly press release. Those switching from Wegovy maintained all but 0.9 kg.
How many people stay on Zepbound after a year?
In a commercial claims analysis, 64.0% of 2023 starters and 64.8% of first-half-2024 starters were still on tirzepatide at one year. In a Military Health System cohort using a more lenient gap definition, 1-year persistence for Zepbound was 81.9%.
What do the trials report about side effects around stopping?
SURMOUNT-4 reported that the most common adverse events were mostly mild-to-moderate gastrointestinal events, occurring more commonly with tirzepatide than placebo during the trial. The BMJ meta-analysis of post-cessation outcomes measured weight and cardiometabolic markers, not individual symptom timelines.
This article summarizes FDA labeling, published research and company information current as of September 14, 2026. It is not medical advice and does not replace a conversation with your own healthcare provider. How we research and verify.