Stopping a GLP-1: Weight Regain, Why It Happens and What to Do

What the trials show when treatment stops

Three studies of the brand-name drugs looked directly at stopping. They differ in design, so treat each result as its own, not as a head-to-head comparison.

These are averages in trial participants and do not describe compounded versions or Gala patients. Individual results vary.

STEP 1 extension (Wegovy)

The STEP 1 trial gave adults without diabetes once-weekly semaglutide 2.4 mg or placebo, plus lifestyle intervention, for 68 weeks. At week 68, treatment and the lifestyle intervention were stopped. An exploratory off-treatment extension followed a subset of 327 participants for another year (Wilding et al., Diabetes, Obesity and Metabolism, 2022).

In that subset, mean weight loss from week 0 to week 68 was 17.3% with semaglutide and 2.0% with placebo. By week 120, people in the semaglutide group had regained 11.6 percentage points of the weight they had lost, leaving a net loss of 5.6% from where they started. The placebo group had a net loss of 0.1%. Most cardiometabolic improvements seen with semaglutide moved back toward baseline. The authors concluded that participants regained two-thirds of their prior weight loss, and that the findings confirm obesity is chronic and suggest ongoing treatment is required to maintain improvements.

Because all analyses in the extension were exploratory and it covered a subset of participants, the numbers are best read as a pattern rather than a precise prediction.

STEP 4 (Wegovy): continuing vs switching to placebo

STEP 4 asked a different question. All participants took semaglutide for a 20-week run-in, losing a mean of 10.6% of body weight. Those who reached the 2.4 mg dose (803 people) were then randomized 2 to 1 to continue semaglutide or switch to placebo for 48 weeks, with lifestyle intervention in both groups (Rubino et al., JAMA, 2021).

From week 20 to week 68, body weight changed by -7.9% with continued semaglutide and +6.9% with placebo, a difference of 14.8 percentage points. The authors concluded that continuing semaglutide led to continued weight loss over the following 48 weeks, compared with switching to placebo.

SURMOUNT-4 (Zepbound): the largest regain

In SURMOUNT-4, adults took tirzepatide at the maximum tolerated dose (10 mg or 15 mg) for 36 weeks, and 670 who completed the lead-in had lost a mean of 20.9% of body weight. They were randomized to continue tirzepatide or switch to placebo for 52 more weeks (Aronne et al., JAMA, 2024).

• From week 36 to week 88, weight changed by -5.5% with continued tirzepatide and +14.0% with placebo, a difference of 19.4 percentage points.
• At week 88, 89.5% of those on tirzepatide had maintained at least 80% of the weight loss achieved during the lead-in, compared with 16.6% of those who switched to placebo.
• Overall weight reduction from week 0 to week 88 was 25.3% with continued tirzepatide and 9.9% with placebo.

The authors concluded that withdrawing tirzepatide led to substantial regain of lost weight, while continued treatment maintained and added to the initial weight reduction.

Why weight comes back

These drugs lower weight by acting on appetite and calorie intake while you take them. The Wegovy and Zepbound labels both state that the medicines decrease calorie intake, likely through effects on appetite. The Wegovy label also says semaglutide stays in the bloodstream for about 5 to 7 weeks after the last injectable dose, and the Zepbound label gives tirzepatide an elimination half-life of about 5 to 6 days. Once the drug is gone, that appetite effect is no longer there.

That is consistent with how the STEP 1 authors describe the results: obesity is a chronic condition, and the benefits depend on continuing treatment. A 2025 joint advisory from four U.S. nutrition and obesity societies says that when GLP-1s are stopped, weight regain is common, typically nearly to baseline within one year, even with conventional nutritional counseling or behavioral therapy. It also points out that whether a more robust, structured nutrition and lifestyle program could reduce regain after stopping has not been studied in controlled trials.

Strategies for maintenance

No strategy has been proven in a controlled trial to prevent regain after stopping, according to that advisory, so the options below are about planning with your provider, not guarantees.

• Ask whether to continue. The labels for Wegovy and Zepbound describe maintenance dosing, and the trials above show the most durable results with continued treatment. Your provider can discuss whether staying on a maintenance dose makes sense for you.
• Do not stop without talking to your provider. If cost, side effects or a health change is behind the decision, your provider can adjust your dose or discuss other options.
• Keep eating and activity routines in place. The advisory lists regular physical activity and self-monitoring of weight, food intake and activity among behaviors associated with long-term weight maintenance. See our guide on what to eat on a GLP-1.
• Protect muscle. The advisory says structured resistance or strength training helps preserve lean mass during weight reduction.
• Track your weight and doses. The Gala GLP-1 app lets you log doses, so you and your care team can see changes early.
• Schedule a follow-up after you stop so that regain, appetite changes and any health measures are reviewed.

Talk to your provider before you stop

Compounded medications are not FDA-approved. Gala offers compounded semaglutide, compounded tirzepatide and brand-name Ozempic®. A licensed provider reviews your online assessment and prescribes only if it is appropriate for you. If prescribed, your medication ships to your home, you can message your care team about stopping or changing your plan, and your provider can adjust your dose.

To see whether a GLP-1 option may be right for you, start your online GLP-1 assessment, or explore the weight loss hub. To understand dose steps, read our GLP-1 dosing schedule guide, and for how the two ingredients compare, see semaglutide vs tirzepatide. You can also read about compounded GLP-1 medications.

This article is for information only and is not medical advice. Talk to your healthcare provider before stopping or changing any prescription medicine.

Sources

1. Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022.
2. Rubino D, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance (STEP 4). JAMA. 2021.
3. Aronne LJ, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity (SURMOUNT-4). JAMA. 2024.
4. Novo Nordisk. WEGOVY (semaglutide) prescribing information. FDA-approved label.
5. Eli Lilly. ZEPBOUND (tirzepatide) prescribing information. FDA-approved label.
6. Mozaffarian D, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint advisory. Obesity Pillars. 2025.

This article is for general information and is not medical advice. Talk to a licensed provider about your own health.