Stopping a GLP-1: what happens next

Many people wonder what happens if they stop semaglutide (Wegovy) or tirzepatide (Zepbound). Clinical trials give a fairly clear answer. On average, people who stopped regained much of the weight they had lost, while people who kept taking the medicine kept most of it off [1, 2, 3].

That doesn’t mean you can never stop. People stop for many reasons, and there are ways to plan for it. This article covers what the research shows, why people stop and which options to talk through with your clinician.

What the trials show

Three trials tested this directly. All of them enrolled adults with obesity or overweight who didn’t have diabetes. The results are averages, so your own experience may differ [1, 2, 3].

STEP 1 extension: stopping semaglutide

In the STEP 1 trial, adults took semaglutide 2.4 mg or a placebo (an inactive look-alike shot) once a week for 68 weeks, along with a lifestyle program. Then both the medicine and the lifestyle program stopped, and a group of 327 participants was followed for another year [1].

Among these 327 people, those on semaglutide had lost an average of 17.3% of their body weight by week 68, compared with 2.0% on placebo. One year after stopping, they had regained about two-thirds of the weight they’d lost. On average, they ended up 5.6% below their starting weight, compared with 0.1% for the placebo group. Most improvements in heart and metabolic risk factors also drifted back toward where they started [1].

STEP 4: continuing or switching to placebo (semaglutide)

In STEP 4, 902 adults started semaglutide in a 20-week run-in, working up to 2.4 mg weekly. The 803 who reached that dose had lost an average of 10.6% of their weight. They were then randomly assigned to keep taking semaglutide or switch to placebo for 48 more weeks, with a lifestyle program in both groups [2].

Over those 48 weeks, people who stayed on semaglutide lost another 7.9% of their weight on average. People switched to placebo gained 6.9%. Waist size and systolic blood pressure (the top number) were also better with continued treatment [2].

SURMOUNT-4: continuing or switching to placebo (tirzepatide)

In SURMOUNT-4, 783 adults started tirzepatide and worked up to the highest dose they could tolerate (10 or 15 mg) during a 36-week phase. The 670 who finished this phase had lost an average of 20.9% of their weight. They were then randomly assigned to keep taking tirzepatide or switch to placebo for 52 weeks, with diet and activity counseling throughout [3, 4].

Over those 52 weeks, people who stayed on tirzepatide lost another 5.5% on average, while weight in the placebo group went up 14.0%. At the end, 89.5% of people who stayed on tirzepatide had kept off at least 80% of the weight they’d lost, compared with 16.6% on placebo. Counting from the very start, average weight loss was 25.3% with continued tirzepatide and 9.9% with placebo [3].

Why many people stay on treatment

Obesity is a chronic (long-term) disease [5]. The STEP 1 researchers said their results confirm this and suggest ongoing treatment is needed to keep the improvements in weight and health [1]. The NIDDK, part of the National Institutes of Health, says your clinician may advise staying on the medicine indefinitely if you’ve lost enough weight to improve your health and aren’t having serious side effects. It also says you’ll probably regain some weight after stopping [5].

In everyday life, though, stopping is common. One study looked at about 125,000 US adults with overweight or obesity who started liraglutide (Saxenda or Victoza), semaglutide or tirzepatide between 2018 and 2023. Within a year, 64.8% of those without type 2 diabetes had stopped, as had 46.5% of those with type 2 diabetes [5, 6].

Reasons people stop

• Side effects. In the main trials, 6.8% of people on Wegovy 2.4 mg stopped because of side effects, vs 3.2% on placebo. For Zepbound, it was 4.8% to 6.7%, vs 3.4% [4, 7]. In the real-world study, moderate or severe stomach and bowel side effects were linked to a higher chance of stopping [6]. See GLP-1 side effects.
• Cost and coverage. Some insurance plans cover these medicines and some don’t [5]. In the real-world study, among people with type 2 diabetes, those with higher incomes were less likely to stop [6]. See GLP-1 medicine costs.
• Pregnancy plans. Weight loss isn’t recommended during pregnancy. Both labels say to stop the medicine once a pregnancy is known. Wegovy’s label says to stop at least 2 months before a planned pregnancy, because semaglutide stays in the body a long time [4, 7]. See GLP-1s, pregnancy and birth control.
• Supply problems. Both medicines were in short supply from 2022 because of high demand, until the FDA declared the shortages over (tirzepatide in late 2024, semaglutide in February 2025). When it ended the semaglutide shortage, the FDA noted that people may still see occasional local supply disruptions [8].
• Not enough benefit. If you haven’t lost at least 5% of your starting weight after 12 weeks on the full dose, the NIDDK says your clinician will probably advise stopping [5].

Options to talk through with your clinician

Staying on treatment

In STEP 4 and SURMOUNT-4, people who kept taking their medicine kept off more weight than people switched to placebo [2, 3]. If the medicine is helping and side effects are manageable, staying on it is one option [5].

A lower maintenance dose, chosen with your clinician

Both labels allow more than one maintenance (long-term) dose: 1.7 mg or 2.4 mg for Wegovy (up to 7.2 mg for some people), and 5 mg, 10 mg or 15 mg for Zepbound. Your clinician chooses based on how well the medicine works for you and how well you tolerate it [4, 7].

One trial tested stepping down. In SURMOUNT-MAINTAIN, 441 US adults took tirzepatide for up to 60 weeks, working up to their highest tolerated dose (10 or 15 mg). At week 60, 378 of them were randomly assigned to stay on that dose, step down to 5 mg or switch to placebo for 52 weeks. Measured from the start of the study, average weight loss at the end was 21.9% with the full dose, 16.6% with 5 mg and 9.9% with placebo [9].

From week 84, people who regained more than half of their lost weight could get “rescue” tirzepatide. This happened in 8% of the full-dose group, 25% of the 5 mg group and 67% of the placebo group. The researchers said 5 mg might be an alternative to stopping, but that responses vary. The trial was funded by Eli Lilly, the maker of Zepbound [4, 9].

A lower dose is a decision to make with your clinician. Use your medicine exactly as prescribed, and don’t lower your dose on your own [4, 7].

More lifestyle support

Healthy eating and regular activity may help you regain less weight after stopping [5]. Federal guidelines recommend at least 150 minutes a week of moderate activity, plus muscle-strengthening activities on at least 2 days. You may need more than 300 minutes a week to keep weight off [5]. Still, in STEP 4 and SURMOUNT-4, people switched to placebo regained weight even though their lifestyle counseling continued [2, 3, 4]. See eating well on a GLP-1.

Other treatments

Your clinician may also suggest other options [5]:

• a different weight management medicine
• a different lifestyle or eating program
• changes to other medicines that can cause weight gain
• a referral to talk about weight-loss (bariatric) surgery

Stopping or restarting safely

Plan any stop with your clinician. The exception is when the labels say to stop right away: signs of pancreatitis (severe stomach pain that won’t go away) or a serious allergic reaction, or a pregnancy [4, 7]. For semaglutide, the UK’s National Health Service (NHS) advises not stopping suddenly. It notes that stopping could affect your blood sugar if you have type 2 diabetes, and that your doctor may suggest lowering the dose gradually [10].

Restarting needs a plan, too. If you miss 2 or more weekly doses of Wegovy in a row, the label says to restart the dose steps at a lower dose to reduce stomach and bowel side effects. Its Medication Guide says to call your clinician about how to restart [7]. Zepbound’s label covers only single missed doses (take it within 4 days, or skip it), so ask your clinician which dose to restart at after a longer break [4]. Either way, don’t restart at your old dose without guidance. For the first weeks back, see starting a GLP-1.

When to get medical care

If you’re stopping because of a side effect, know the warning signs. Stop the medicine and call your clinician right away for severe stomach pain that won’t go away, with or without vomiting. Call 911 for swelling of your face, lips, tongue or throat, or trouble breathing or swallowing [4, 7, 11]. If you have type 2 diabetes, keep in mind that these medicines lower blood sugar [4, 7], and the NHS notes that stopping semaglutide could affect it [10]. Ask your clinician how to watch your blood sugar after you stop.

The bottom line

In trials, people who stopped semaglutide or tirzepatide regained, on average, a large share of the weight they had lost within a year, while those who kept taking it kept most of it off. That’s one reason obesity is treated as a long-term condition and many people stay on treatment. If you want or need to stop, plan it with your clinician. Options may include a lower maintenance dose for some people, more lifestyle support or a different treatment. Unless a label says to stop right away, such as for signs of pancreatitis, a serious allergic reaction or pregnancy, don’t stop on your own, and don’t restart at a high dose without guidance.

References

1. Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes, Obesity and Metabolism. 2022. https://pubmed.ncbi.nlm.nih.gov/35441470/
2. Rubino D, et al. 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. 2021. https://pubmed.ncbi.nlm.nih.gov/33755728/
3. Aronne LJ, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: the SURMOUNT-4 randomized clinical trial. JAMA. 2024. https://pubmed.ncbi.nlm.nih.gov/38078870/
4. Eli Lilly and Company. ZEPBOUND (tirzepatide) injection, for subcutaneous use: prescribing information, Medication Guide and Instructions for Use. DailyMed, U.S. National Library of Medicine. Label revised August 2026 (effective August 28, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b
5. National Institute of Diabetes and Digestive and Kidney Diseases. Prescription medications to treat overweight and obesity. NIDDK, National Institutes of Health. Last reviewed June 2024. https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity
6. Rodriguez PJ, et al. Discontinuation and reinitiation of dual-labeled GLP-1 receptor agonists among US adults with overweight or obesity. JAMA Network Open. 2025. https://pubmed.ncbi.nlm.nih.gov/39888616/
7. Novo Nordisk. WEGOVY (semaglutide) injection, for subcutaneous use; WEGOVY (semaglutide) tablets, for oral use: prescribing information, Medication Guide and Instructions for Use. DailyMed, U.S. National Library of Medicine. Label revised June 2026 (effective June 18, 2026). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b
8. U.S. Food and Drug Administration. FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. FDA. Content current as of April 1, 2026. https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize
9. Horn DB, et al. Tirzepatide for maintenance of bodyweight reduction in people with obesity in the USA (SURMOUNT-MAINTAIN): a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2026. https://pubmed.ncbi.nlm.nih.gov/42119587/
10. NHS. Semaglutide: a medicine to manage type 2 diabetes or treat obesity. NHS website. Page last reviewed May 2026. https://www.nhs.uk/medicines/semaglutide/
11. MedlinePlus. Anaphylaxis. U.S. National Library of Medicine. Last updated December 2025. https://medlineplus.gov/anaphylaxis.html

This article is for education only and isn’t a substitute for advice from your own clinician.