What studies show after stopping a GLP-1

How the trials tested stopping

Two designs were used. The STEP 1 extension followed a subset of STEP 1 participants for a year after semaglutide 2.4 mg and the trial’s lifestyle programme ended together at week 68 ^[1]. STEP 4 and SURMOUNT-4 used randomised withdrawal: everyone took the medicine first, then part of the group was switched, without knowing it, to placebo, while lifestyle counselling continued for all ^[2][3].

The designs answer slightly different questions. The extension shows what happened when medicine and support stopped at the same time. The withdrawal trials compare continuing with stopping under otherwise equal conditions. All three report group averages from people who tolerated the medicine well enough to stay in, and none says what will happen to one person.

What else the three trials measured

• STEP 1 extension: the participants came from sites in Canada, Germany, the UK, the US and Japan, and the authors called every analysis exploratory. Most of the cardiometabolic improvements seen on treatment moved back towards baseline by week 120 ^[1].
• STEP 4: waist size, systolic blood pressure and a physical functioning score also favoured continued treatment. Stomach and bowel events were reported by 49.1% of those continuing semaglutide and 26.1% of those on placebo, and similar shares stopped because of side effects (2.4% and 2.2%) ^[2].
• SURMOUNT-4: at week 88, 89.5% of those still on tirzepatide had kept at least 80% of their earlier loss, against 16.6% on placebo. Across all 88 weeks the mean loss was 25.3% with continued tirzepatide and 9.9% in the group switched to placebo ^[3]. The Zepbound® label adds that 14.4% of people stopped before randomisation, most often because of adverse events ^[7].

What reviews of many trials add

Two meta-analyses have pooled randomised trials that followed people after a GLP-1 medicine was withdrawn. A meta-analysis combines results from several studies; it gives a more stable average, but it cannot remove the differences between the trials it pools.

• Tzang and colleagues, 2025: 18 trials with 3,771 participants and at least 12 weeks of follow-up after stopping. In people with obesity, body weight rose by a mean 5.63 kg and HbA1c by 0.25 points; in type 2 diabetes, weight rose by 2.03 kg and HbA1c by 0.65 points. Regain was larger with follow-up beyond 26 weeks and after semaglutide than after liraglutide ^[4].
• Berg and colleagues, 2025: 8 trials with 2,372 participants. People regained a mean 2.20 kg after liraglutide and 9.69 kg after semaglutide or tirzepatide, and the amount regained was proportional to the amount lost ^[5].
• Limits: in the larger review, results varied widely from one trial to the next, and both reviews report averages from trial populations that received structured support ^[4][5].

What the product information says about stopping

• Purpose: Wegovy® and Zepbound® are approved to reduce excess body weight and to maintain weight reduction long term, together with a reduced-calorie diet and more physical activity ^[6][7].
• No step-down: the dosing sections describe a starting dose, increases, missed doses and restarts. None of the US labels or EU documents cited here describes reducing the dose gradually to stop ^{[6][7][8][9][10][11]}.
• Talk first: the EU leaflets ask you not to stop without talking to your doctor, and for Ozempic®, and Mounjaro® in type 2 diabetes, they add that blood sugar can rise once treatment stops ^[10][11].
• The medicine lingers: the Wegovy® label estimates that semaglutide is still circulating roughly 5 to 7 weeks after a final dose, and the Zepbound® label gives tirzepatide a half-life of about 5 to 6 days ^[6][7].
• Coming back after a gap: the Wegovy® label restarts escalation at a lower dose after 2 or more missed weekly doses, the Saxenda® label at 0.6 mg after more than 3 days, and the Foundayo™ label at a lower dose after 7 or more missed tablets in a row ^[6][8][9].

When the labels themselves say to stop

• Suspected pancreatitis: the labels ask for the medicine to be stopped if pancreatitis is suspected. The Wegovy® Medication Guide describes the warning sign as intense pain in the stomach area that persists, which can reach through to the back and may or may not come with nausea or vomiting ^[6].
• A serious allergic reaction, such as swelling of the face, lips, tongue or throat: stop and get medical help straight away ^[6].
• Pregnancy: the Wegovy®, Zepbound® and Foundayo™ labels say to stop when a pregnancy is recognised, and the Wegovy® label asks for semaglutide to be stopped at least 2 months before a planned pregnancy ^[6][7][9]. The EU Mounjaro® document gives at least 1 month for tirzepatide ^[11].
• Not enough response: the US Saxenda® label asks for weight to be checked 16 weeks after starting and treatment stopped below a 4% loss, or if the 3 mg dose is not tolerated ^[8]. The EU Saxenda® document uses 12 weeks on 3.0 mg and a 5% threshold ^[12]. The NIDDK gives a similar general rule of thumb for weight medicines: less than 5% after 12 weeks on the full dose ^[13].
• Heart rate: the Wegovy® label asks for treatment to be stopped if resting heart rate stays raised ^[6].

Breaks that are not a full stop

Treatment is often interrupted rather than ended: by surgery, illness, travel, cost or supply. For procedures, the Wegovy® label says the available data are insufficient to say whether pausing the medicine reduces the risk of food remaining in the stomach during anaesthesia, and asks you to tell the team about any planned surgery or procedure ^[6]. The article on surgery and anaesthesia covers that in more detail.

Coming back after a break is where the restart rules above apply. Taking up the old dose after several missed weeks is not what the Wegovy® label describes, and its Medication Guide asks you to contact your healthcare provider about how to restart ^[6].

If you are thinking about stopping

The NIDDK describes two paths. If a weight medicine has improved your health without serious side effects, your health professional may advise staying on it indefinitely; if you stop, you will probably regain some weight, and healthy eating and more activity may help you regain less ^[13].

That conversation goes better with facts in hand: the date of your last dose, the dose you were on, how your weight has changed since you started, which side effects you had and for how long, and, if you have diabetes, your recent glucose readings. Whether to continue, pause or stop is decided with your prescriber.

Wegovy®, Ozempic® and Saxenda® are registered trademarks of Novo Nordisk A/S. Zepbound® and Mounjaro® are registered trademarks and Foundayo™ is a trademark of Eli Lilly and Company. PepLabo is not affiliated with or endorsed by Novo Nordisk or Eli Lilly and Company.

When to get help