# The Weight Comes Back. What the GLP-1 Trials Say About Stopping > Semaglutide and tirzepatide produce weight loss that once required surgery. The trial data on stopping them is just as important, and it should shape how people plan to use them. - Publication: New England Anti-Aging (https://newenglandantiaging.com) - Department: The Long Read - Label: Analysis - Section: Metabolism - Author: Priya Raman, Staff Writer, Metabolism and Food - Published: 2026-11-06 - Lead photograph: A hand holding an injection pen, by Sweet Life on Unsplash (https://unsplash.com/photos/a-person-holding-an-insulin-injection-0rXHOonM9Ug) - Canonical URL: https://newenglandantiaging.com/metabolism/what-happens-when-you-stop-a-glp-1/ ## The Short Version - In STEP 1, people regained about two-thirds of their lost weight within a year of stopping semaglutide. - In SELECT, semaglutide cut major cardiovascular events by 20 percent in adults with heart disease and excess weight. - Protecting muscle with protein and strength training is now a standard part of a good GLP-1 plan. The first wave of GLP-1 stories was about what the drugs could do. The second wave is about what happens after. As millions of people have started semaglutide or tirzepatide, a practical question has moved to the center of obesity medicine. Is this a course of treatment, like an antibiotic, or a long-term therapy, like a blood pressure pill? The trial data points firmly toward the second answer. That is not a reason to avoid these drugs. It is a reason to start them with a plan. ## How well they work In the [STEP 1 trial](https://doi.org/10.1056/NEJMoa2032183), 1,961 adults with obesity or overweight plus a weight-related condition took weekly semaglutide 2.4 milligrams or a placebo for 68 weeks, alongside lifestyle counseling. The semaglutide group lost an average of about 15 percent of body weight. The placebo group lost about 2 percent. Tirzepatide, which acts on both GLP-1 and GIP receptors, pushed further. In [SURMOUNT-1](https://doi.org/10.1056/NEJMoa2206038), adults on the highest dose lost about 21 percent of body weight on average over 72 weeks. The benefits extend beyond the scale. The [SELECT trial](https://doi.org/10.1056/NEJMoa2307563) enrolled more than 17,000 adults with established cardiovascular disease and overweight or obesity, but no diabetes. Semaglutide reduced the combined rate of cardiovascular death, heart attack and stroke by 20 percent compared with placebo. ## The data on stopping The clearest look at discontinuation comes from two follow-up studies. In the [STEP 1 extension](https://doi.org/10.1111/dom.14725), a subset of 327 participants was followed for a year after everyone stopped their assigned treatment and lifestyle program at week 68. People who had taken semaglutide had lost an average of 17.3 percent of body weight while on the drug. One year after stopping, they had regained about two-thirds of it. Improvements in blood pressure, blood sugar and cholesterol drifted back toward where they started. [STEP 4](https://doi.org/10.1001/jama.2021.3224) asked the question in a cleaner way. All participants took semaglutide for 20 weeks and lost about 10.6 percent of body weight. Then they were randomly split. Those who kept taking the drug lost about 7.9 percent more over the next 48 weeks. Those switched to placebo regained about 6.9 percent. > These drugs do not cure obesity. They treat it, in the same way a statin treats high cholesterol. The researchers' interpretation was direct. Obesity behaves like a chronic disease. When the treatment stops, the biology that drove weight gain in the first place, including appetite signals that ramp up after weight loss, comes back. ## What that means in practice None of this means stopping is always wrong. People stop for cost, side effects, supply problems, pregnancy plans or simply preference. What the data suggests is that stopping should be a planned transition rather than an abrupt end. Clinicians are increasingly approaching this in a few ways. Some patients taper to a lower maintenance dose rather than stopping outright. Some extend the interval between doses. Others step down while deliberately strengthening the habits that help hold weight, particularly regular physical activity, which is consistently one of the best predictors of weight maintenance. None of these strategies has the depth of evidence that the main trials do, so they work best as monitored experiments with a clinician rather than solo adjustments. ## The muscle question Weight lost on a GLP-1 is not all fat. In a body composition substudy of STEP 1, close to 40 percent of the weight lost was lean mass, a category that includes muscle along with water and organ tissue. That ratio is broadly similar to what happens with other forms of significant weight loss, but the speed and scale of GLP-1 weight loss make it more consequential, especially for older adults who are already [fighting the slow drift of sarcopenia](/longevity/muscle-is-the-organ-of-aging-well/). The countermeasures are not exotic. Adequate protein, often in the range of 1.0 to 1.2 grams per kilogram of body weight for older adults unless kidney disease limits it, matters more when appetite is suppressed and meals get small. Resistance training two or three times a week gives the body a reason to hold on to muscle. A body composition scan at the start and at intervals shows whether the plan is working. ## Questions worth asking before you start A good GLP-1 consultation covers more than the dose schedule. It should cover what success looks like beyond weight, such as blood pressure, glucose, liver health and fitness. It should include a nutrition plan for eating less while still eating enough protein, fiber and micronutrients. It should address side effects, which most often are nausea, constipation and other digestive symptoms that tend to ease over time. It should have a strategy for the long term, including what happens if insurance coverage changes. The trials also leave real gaps. Most stopping studies ended treatment abruptly, while many people in the real world taper, skip doses when supplies run short or switch drugs. Researchers are only beginning to study those patterns. Until that data arrives, anyone planning to stop should do it with a clinician who can track weight, blood pressure and glucose for the months that follow. ## What the Evidence Doesn't Settle The major semaglutide and tirzepatide trials were funded by their manufacturers, and follow-up beyond a few years is still limited. Strategies such as tapering or stretching the time between doses are being used in clinics but have far less trial evidence than continuous treatment. Cost and insurance coverage often decide whether people stay on these drugs, regardless of what the data suggest. ## Notes and Sources 1. Once-Weekly Semaglutide in Adults With Overweight or Obesity (STEP 1). New England Journal of Medicine, 2021. https://doi.org/10.1056/NEJMoa2032183 2. Weight Regain and Cardiometabolic Effects After Withdrawal of Semaglutide, the STEP 1 Trial Extension. Diabetes, Obesity and Metabolism, 2022. https://doi.org/10.1111/dom.14725 3. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance (STEP 4). JAMA, 2021. https://doi.org/10.1001/jama.2021.3224 4. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine, 2022. https://doi.org/10.1056/NEJMoa2206038 5. Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes (SELECT). New England Journal of Medicine, 2023. https://doi.org/10.1056/NEJMoa2307563 --- Published by New England Anti-Aging, the health and longevity magazine of Align Wellness, 250 Centerville Rd, Building E, Warwick, RI 02886. General information only, not medical advice.