By Dr. Asnat Raziel, bariatric surgeon specializing in obesity treatment, metabolic health and healthy longevity; Director of the Multidisciplinary Center for Obesity Treatment, Assia Medical, Assuta Ramat HaChayal, Tel Aviv
Tapering semaglutide: an important question, still without an answer
Is tapering semaglutide better than stopping it all at once? The REST trial asks a question many of my patients ask me: what happens when you stop semaglutide after successful weight loss? Is it better to stop at once, or to lower the dose gradually to give the body time to adjust? In July 2026, the researchers published the trial protocol, meaning its work plan, in the journal PLOS One.
It is important to stress this right from the start: this is a study design, not a study with results. According to the protocol, recruitment began in March 2026, data collection will end in July 2028, and results should arrive in 2030. So we cannot conclude from it that gradual dose reduction prevents weight regain. That is exactly the hypothesis the trial sets out to test.
Its full name is Recovery Effects after Semaglutide Termination, and it is registered in the clinical trials database. Researchers from Mount Sinai Hospital and the University of Toronto in Canada are leading the trial.
Why does weight come back after treatment stops?
Semaglutide, the active ingredient in Wegovy, mimics the satiety hormone GLP-1. The drug reduces hunger, increases fullness and affects eating regulation. In the STEP 1 trial, patients lost an average of 14.9% of their body weight after 68 weeks. In addition, blood pressure, blood sugar and blood fats improved.
However, after an abrupt stop, many patients regain weight. In the STEP 1 extension study, participants regained about two-thirds of the weight they had lost within a year. Most of the metabolic improvements also drifted back toward their starting values. Building on this, a meta-analysis published in the BMJ in January 2026 pooled 37 studies with 9,341 participants. According to the analysis, average weight regain reached 0.4 kg a month, and metabolic markers are expected to return to baseline within about 1.4 years.
The reason is not a “lack of discipline.” Weight loss triggers biological defense mechanisms that protect the body’s energy stores. Hunger rises, energy expenditure falls, and hunger and satiety hormones shift in a direction that encourages eating. When the drug stops working, these mechanisms become especially prominent. I wrote about what happens to appetite at this stage in my article on stopping weight loss medication.
The REST trial hypothesis on tapering semaglutide
Most studies to date have compared continuing treatment with stopping abruptly. Almost no randomized trial has examined the best way to stop when stopping is necessary. The researchers hypothesize that tapering the dose gradually over 16 weeks will soften the body’s compensatory response. In other words, the hunger, satiety and energy expenditure systems will get time to adapt. The hypothesis makes biological sense, but it has not yet been proven.
How will the REST trial on tapering semaglutide work?
This is a randomized, controlled, open-label trial with two groups at a single center in Toronto. Each participant will stay in the trial for 32 weeks. During the first 16 weeks, participants will follow their assigned stopping strategy. For the next 16 weeks, all participants will be off the drug.
- Abrupt-stop group: participants continue at the full dose for 16 weeks, and then stop all at once.
- Gradual-taper group: the dose drops by 25% every four weeks, until it stops completely at week 16.
All participants will receive standard lifestyle advice: physical activity, portion control and self-weighing. On the other hand, the protocol does not describe an intensive behavioral program, such as regular sessions with a dietitian or structured strength training.
Who will take part?
The trial will include 98 men and women aged 18 to 75, with a BMI of 30 or higher, or 27 or higher with a complication such as high blood pressure or fatty liver. Participants must be on a weekly semaglutide injection of at least 1 mg. In addition, they must have lost at least 10% of their body weight and kept their weight stable over the past 12 weeks.
By contrast, the trial will exclude people with type 2 diabetes, previous heart disease, heart failure, past bariatric surgery, an eating disorder, pregnancy or breastfeeding. This means the results will not necessarily apply to these groups.
What will the researchers measure?
The primary outcome is the difference in percentage weight change 16 weeks after the complete stop. The researchers designed the trial to detect a 3% difference between the groups. For example, for a person who weighs 90 kg, 3% is about 2.7 kg.
In addition, the researchers will measure continuous blood pressure over 24 hours and fasting ghrelin levels. Ghrelin is often called the “hunger hormone,” because it stimulates appetite and food seeking. Participants will also undergo a standard meal test. Afterward, the researchers will check the blood response of the hunger and satiety hormones: ghrelin, PYY, GLP-1, GIP and glucagon. At the same time, participants will rate their own feelings of hunger.
What do we already know about tapering the dose?
Meanwhile, data have arrived from a related trial that tested stepping down to a maintenance dose rather than stopping completely. In the SURMOUNT-MAINTAIN trial, published in The Lancet in May 2026, participants received tirzepatide at the maximum dose for 60 weeks. The researchers then split them into three groups: continuing the maximum dose, stepping down to 5 mg or switching to placebo.
After 112 weeks, total weight loss stood at 21.9% on the maximum dose, 16.6% on 5 mg and 9.9% on placebo. From the point of randomization, weight remained stable on the maximum dose, rose by 7.0% on 5 mg and rose by 15.2% on placebo. In other words, a low dose preserved much of the result, but less than the full dose. This is important information, but it does not answer the REST trial’s question: what happens when you stop completely?
Strengths and limitations
The main strength is randomization. It reduces the chance that differences stem from motivation or from different health status. In addition, the trial looks not only at weight but also at blood pressure, hormones and metabolic markers, so it may help explain the mechanism.
On the other hand, the trial is small and runs at a single center. Participants know which group they are in, and this may affect their eating and how they report hunger. The drug-free follow-up is also short, only 16 weeks. Finally, weight stability at entry relies on self-report and allows a change of up to 5%.
What does the REST trial on tapering semaglutide tell us right now?
The trial shows that science is moving from a simple question, “Does the drug lower weight?”, to more complex ones: who needs long-term treatment, whether doctors can reduce the dose, and how to stop as safely as possible. Even so, the protocol does not prove that a gradual taper is better. Therefore, you should not treat it as a recommendation to reduce your dose on your own, without medical follow-up.
Stopping treatment should be a personal decision. It depends on the reason for stopping, the amount of weight lost, your hunger level, underlying conditions and body composition. It is worth preparing for it in advance, with a protein-rich diet, strength training, good sleep and close follow-up. I have expanded on this in my articles on preparing to stop treatment from the very start and on gradually stopping weight loss medications.
The bottom line on tapering semaglutide
The key message of the REST trial is not that we have found the right way to stop semaglutide. Rather, it is that researchers are testing this question in a randomized, systematic way for the first time. Until the results arrive, the evidence continues to show that obesity is a chronic disease. For many people, stopping the drug comes with returning hunger and weight regain. That is why reaching your goal weight is not the end of treatment, but a transition to a long-term maintenance plan tailored to each patient.
The information in this article is general and does not replace personal medical advice.
References
Once-Weekly Semaglutide in Adults with Overweight or Obesity
The Heart and Stroke Foundation of Canada funds the REST trial. According to the researchers, the funder has no role in the design, analysis or publication. Lilly, the maker of tirzepatide, funded the SURMOUNT-MAINTAIN trial.
