# GLP-1 Withdrawal Trials: STEP 1, STEP 4 and SURMOUNT-4 Compared | This GLP STEP 1, STEP 4 and SURMOUNT-4 each measured what happens when a GLP-1 drug is withdrawn: the regain figures, the spread behind them, and what they mean for a prepaid plan. Publisher: This GLP Editorial Team Canonical: https://thisglp.com/research/stopping-glp1-and-weight-regain Updated: 2026-10-26 Published: 2026-09-15 [← Research](https://thisglp.com/research) Evidence # GLP-1 Withdrawal Trials: STEP 1, STEP 4 and SURMOUNT-4 Compared Three randomized withdrawal studies measured what happens after the drug stops. In the STEP 1 extension, participants regained two thirds of the loss within a year. [This GLP Editorial Team](https://thisglp.com/about)September 20267 min readUpdated September 2026 On treatment · Stopped · Two thirds of the loss came back within a year. **Research, not medical advice.** This GLP is independent and educational. Nothing here is a substitute for individualized care from a licensed clinician, and reading it creates no doctor–patient relationship. Talk to your own provider before starting, stopping, or changing any medication, peptide, or therapy. See our [methodology](https://thisglp.com/methodology) and [terms](https://thisglp.com/terms). Everything a reader is asked to decide about price — a month at a time or a year up front, a three-month bundle or a rolling plan — turns on one question that the pricing pages never answer. Is this a course of treatment that ends, or a medication taken indefinitely? Three randomized withdrawal studies have asked it directly, and they agree with each other more closely than most bodies of evidence ever do. ## STEP 1, one year after the drug stopped The STEP 1 extension followed 327 participants for a year after semaglutide 2.4 mg and lifestyle support were withdrawn. Mean weight loss to week 68 had been 17.3% on semaglutide against 2.0% on placebo. By week 120, the semaglutide group had regained 11.6 percentage points of what they lost, leaving a net loss of 5.6% from where they started[\[1\]](https://thisglp.com/research/stopping-glp1-and-weight-regain#ref-1). Cardiometabolic improvements reverted toward baseline for most variables over the same period. Two thirds of the loss came back in twelve months. The third that stayed is real, and it matters, and it is not what the headline figure describes. A reader deciding whether to buy a year at a [prepaid rate](https://thisglp.com/reviews/leanmeds) is deciding in month one about a trajectory that is only visible at month 120. ## STEP 4 separated continuing from stopping STEP 4 ran a 20-week open-label lead-in on semaglutide, then randomized the 803 participants who reached the 2.4 mg maintenance dose to continue or to switch to placebo for 48 weeks. From week 20 to week 68, the continuing group lost a further 7.9% while the placebo group gained 6.9%, a difference of 14.8 percentage points (95% CI −16.0 to −13.5)[\[2\]](https://thisglp.com/research/stopping-glp1-and-weight-regain#ref-2). Both groups kept the same lifestyle support throughout. That design is what makes the finding hard to argue with. The two arms had the same starting weight, the same behavior program and the same twenty weeks of history behind them, and the only difference after randomization was whether the drug continued. Those twenty weeks are the escalation window the [titration evidence](https://thisglp.com/research/how-long-does-nausea-last-on-a-glp1) describes. ## SURMOUNT-4 found the same thing with tirzepatide SURMOUNT-4 gave 783 adults an open-label 36-week lead-in on the maximum tolerated dose of tirzepatide, producing a mean reduction of 20.9%, then randomized 670 of them to continue or to switch to placebo for 52 weeks. From week 36 to week 88 the continuing group changed by −5.5% and the placebo group by +14.0%, a difference of 19.4 percentage points[\[3\]](https://thisglp.com/research/stopping-glp1-and-weight-regain#ref-3). At week 88, 89.5% of those still on tirzepatide had kept at least 80% of the lead-in loss, against 16.6% of those switched to placebo. ## What the three studies together do and do not establish They establish that stopping is followed by regain, on both molecules, in randomized conditions, with lifestyle support held constant. They do not establish that everyone regains, that the rate is the same for everyone, or that a person who stops after reaching a goal cannot hold any of it. Group means are group means, and the STEP 1 extension’s standard deviation of 7.7 percentage points on the regain figure says plainly that the spread was wide. They also do not tell a reader how long to stay on. That is a clinical decision made with a prescriber, and the practical version of it is often about cost rather than medicine. The [cost calculator](https://thisglp.com/tools/glp1-cost-calculator) is the honest place to work out what an indefinite prescription costs at the dose you expect to sit on, rather than at the entry dose the advertisement is written around. ## What this means for a prepay decision If the evidence said treatment was a course, buying twelve months at a discount would be buying the whole thing. It says the opposite, so a twelve-month prepay is a discount on the first part of something longer, taken before the reader knows whether they tolerate the drug or reach a plateau. A month-to-month rate costs more per month and keeps that decision open, which is why the [seller reviews](https://thisglp.com/reviews) record the standing rate rather than the prepaid rung wherever a seller publishes both. The billing model can leave more or less room to reassess. [Contour Health](https://thisglp.com/reviews/contour-health) says in its [FAQ](https://www.contourhealthrx.com/faqs) that weight-loss medication is purchased by the vial without a subscription. That is a purchasing distinction, not evidence that stopping treatment is easier or that its patients avoid regain. ## Frequently asked How much weight comes back after stopping? In the STEP 1 extension, participants regained 11.6 of the 17.3 percentage points they had lost within a year of withdrawal, leaving a net 5.6% below their starting weight. Does continuing treatment prevent it? In STEP 4 the continuing group lost a further 7.9% while the placebo group gained 6.9% over the same 48 weeks. In SURMOUNT-4, 89.5% of those continuing tirzepatide kept at least 80% of the lead-in loss, against 16.6% on placebo. Does everyone regain? The studies report group means, and the spread around them is wide. The STEP 1 extension reported a standard deviation of 7.7 percentage points on the regain figure, so individual results varied considerably. ## Sources 1. \[1\] Wilding JPH, Batterham RL, Davies M, et al. (2022). Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension Diabetes, Obesity and Metabolism. [PMID 35441470](https://pubmed.ncbi.nlm.nih.gov/35441470/) 2. \[2\] Rubino D, Abrahamsson N, Davies M, et al. (2021). Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial JAMA. [PMID 33755728](https://pubmed.ncbi.nlm.nih.gov/33755728/) 3. \[3\] Aronne LJ, Sattar N, Horn DB, et al. (2024). Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial JAMA. [PMID 38078870](https://pubmed.ncbi.nlm.nih.gov/38078870/) ## Where to get it ### Best GLP-1 injections Every injectable seller we can verify, with the price each one publishes and an honest read of what the trials measured. [Compare providers →](https://thisglp.com/best/compounded-semaglutide) ## More in Evidence - [ 150 minutes · Weekly activity goal · 2 days · Muscle strengthening · Adapt · Symptoms and ability ### Exercise on Ozempic: Building Strength Without Ignoring Symptoms ](https://thisglp.com/research/exercise-on-ozempic) - [ STEP 1, semaglutide 2.4 mg vs placebo, % change at 68 weeks · LDL cholesterol · −2.5% vs +1.3% · Total cholesterol · −3.3% vs +0.1% · HDL cholesterol · +5.2% vs +1.4% · Triglycerides · −21.9% vs −7.3% · Wegovy label, Table 13. Adults without diabetes. Ozempic doses are lower. ### Does Ozempic Lower Cholesterol? What the Lipid Results in the Trials Show ](https://thisglp.com/research/does-ozempic-lower-cholesterol) - [ Where the insulin reduction came from, units per day · week 4 · 13.4 total · week 26 · 21.9 · the drug itself · the weight loss · The drug’s own contribution barely moved: 11.1 then 11.4. · Everything added between weeks 4 and 26 came from weight. ### Does Semaglutide Help Type 1 Diabetes? What Two Small Trials Found ](https://thisglp.com/research/semaglutide-in-type-1-diabetes)