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March 4, 20257 min readMost People Stop Ozempic after Two Years. What Happens to Weight and Health?Ozempic and similar GLP-1 weight-loss medications are designed to be a lifelong treatment. But a new study finds the majority of people who use these drugs quit after just two yearsBy Lori Youmshajekian edited by Lauren J. Young David Petrus Ibars/Getty ImagesThe class of weight-loss drugs including semaglutide, sold as Wegovy, have become immensely popular new treatments for obesity. One key factor in their effectiveness is that people need to take them indefinitelybut in practice, many dont. A recent JAMA Network Open analysis found the vast majority of people quit taking these drugs within two yearssuch stops in treatment often reverses weight loss and health gains. Many people who use these drugs, and clinicians who prescribe them, are questioning how sustainable they areand what quitting them might do to long-term health.Growing evidence shows that many people can be considered overweight and healthy, but the relationship between health and weight is complex.Obesity can be associated with an increased risk of severe illness. The new medications, technically known as glucagon-like peptide 1 (GLP-1) receptor agonists, are used to promote substantial weight loss, cause a host of cardiometabolic improvements and treat type 2 diabetes. (Drugs for the latter include a form of semaglutide sold as Ozempic.) But when a person who had been taking one of these medications stops, the hunger cues it had suppressed often come raging back, which causes the weight to return. Other health benefits of the drugs, such as reduced blood pressure, also tend to bounce back after stopping treatment. Some evidence suggests that certain cardiometabolic benefits may persist but only modestly.Thenew study surveyed more than 120,000 people, with and without type 2 diabetes, who were taking a GLP-1 medication. All were considered overweight or had obesity, and 61 percent had type 2 diabetes.The researchers found that half of the participants stopped treatment within a year of starting it, and nearly three quarters did so by the second year. The drop-off was even higher among those without type 2 diabetes: 85 percent quit after two years. The study did not investigate the effects of ceasing to use a GLP-1 medication, but previous human investigations have found that regaining weight is almost inevitable.On supporting science journalismIf you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today.These drugs work by mimicking gut hormones that slow digestion and signal to the brain that the body is full, ultimately curbing the urge to eat. But the food noise comes back when they stop the medications, says Janice Jin Hwang, an associate professor of medicine and chief of the division of endocrinology and metabolism at the University of North Carolina School of Medicine.Keeping weight off isnt as simple as ignoring food cravings; some research suggests that the human body doesnt seem to like losing weight and actively works against it. One explanation for this is what researchers call the set point theory, which suggests that each person has a specific weight range their body naturally tries to maintain. When you start to lose weight, your body actually adapts to try to hold on to the weight, Hwang explains. A cascade of biological responses kicks in as the body tries to defend its weight: the gut begins secreting hormones that nudge up appetite and make food taste more rewarding. At the same time, the body burns fewer calories while resting.This pattern of weight regain is reflected in clinical trials and studies that tracked people after they ended the treatment. A 2022 clinical trial followed about 200 people who had taken semaglutide for more than a year and lost an average of 17 percent of their body weight. When a subset of these participants stopped receiving the drug, they regained about 12 percent of their body weight within a year. They still experienced a net 5 percent weight lossa number considered clinically meaningful. As little as 3 percent weight loss can have a meaningful benefit for diabetes, hyperglycemia and dyslipidemia (abnormal lipid levels in the bloodstream, which poses a higher risk for cardiovascular disease)but these conditions, along with many others, often require a greater amount of weight loss to lead to health improvements.Even after quitting GLP-1 treatments, however, youre still getting at least some benefit [with at least 5 percent weight loss], which is great, says Chika Anekwe, an obesity medicine physician at Massachusetts General Hospital Weight Center, but not the entire benefit that you would if you could keep off the majority of the weight.Other studies paint a similar picture. In a short 2021 trial, people who stopped semaglutide after 20 weeks regained most of their lost weight after almost a year but still ended up about 4 percent below their starting weight. And compared with the 2022 study, the participants of this earlier investigation gained weight back at a slower pace. The 2021 trials researchers speculated that continued lifestyle interventions, such as a calorie-controlled diet and exercise, may have helped to slow the rate. In another study from 2023 in which people were given tirzepatidea newer drug that targets GLP-1 and a similar metabolic hormone called glucose-dependent insulinotropic polypeptide (GIP)participants kept off almost 10 percent of their weight a year after they stopped taking the medication. But in all these examples, its unclear whether the weight loss would remain in the longer term.It could be that, given more [observational] time, they would have gone back to their baseline weight, says Nia Schwann Mitchell, an associate professor of medicine and a medical weight management specialist at Duke University.Researchers have also noted that GLP-1 receptor agonists treat more than just obesity. The drugs were originally developed as a type 2 diabetes medication and have been shown to improve several metabolic markers such as blood sugar, blood pressure and cholesterol levels. The Food and Drug Administration has also approved Wegovy as a treatment for heart disease, and Ozempic as a treatment to reduce risks of chronic kidney disease. And evidence suggests stopping the drugs seems to reverse many of those health benefits as well.In the 2022 semaglutide trial, participants blood pressure readings went back up to pretreatment levels after they stopped taking the medication. Some biological markers, such as cholesterol and C-reactive protein (a measure of inflammation), remained slightly improved. For people who started the trial with prediabetes, only 6 percent still had this condition after taking the drugbut a year after stopping, many of them had reverted to prediabetic status.Interestingly, the 2022 trial revealed that any benefits that persisted after quitting depended on the magnitude of the initial weight loss. The more people lost, the more likely they were to retain modest health improvements, even after gaining some weight back. This reflects earlier findings among people with type 2 diabetes who lost weight after intensive lifestyle interventions: those who lost more weight still had improved hemoglobin A1c levels (a measure of blood sugar) after four years, even after regaining all the weight.Without a longer follow-up, however, its difficult to determine whether any of these lingering changes will last. This isnt a cure; this is a treatment, Anekwe says. Youre withdrawing the treatment, and the disease is going to come back. Thats what we pretty much see.Some clinicians are seeking answers on how changing dosages might help people maintain their health and weight goals once they reach them. Can we reduce the dose? Can we give them the dose every other week? Mitchell says. We dont know. Early data presented in May 2024 at the European Congress on Obesity suggest that tapering the medication over nine weeks led to a stable body weight six months later. If these early results hold up in replicated trials, that could mean people might not need the treatment indefinitely. But Anekwe says its still too early to draw conclusions from the study, which was small and has yet to be peer-reviewed.Anecdotally, we can see that the rebound hunger is stronger when you stop suddenly versus tapering, Anekwe says. But I dont believe thats been studied in a rigorous way.Rather than developing a dosage off-ramp, other experts argue that these drugs should be treated like any other chronic disease medication. No one would say that blood pressure medication should be stopped once your blood pressure is under control, says Sadiya Khan, a professor of cardiovascular epidemiology and preventive cardiologist at the Northwestern University Feinberg School of Medicine, who co-authored a JAMA editorial that made a case for more research to understand why people quit.A multitude of factors contribute to the high discontinuation rates, but one stands out as the primary reason: the cost. Insurance might be playing a really important role here, says Tricia Rodriguez, lead author of the recent JAMA Network Open study and a principal applied research scientist at Truveta Research, a company using health care data to inform health economics research, monitor safety and support clinical trials. People without type 2 diabetes have a harder time getting insurance coverage for these medications, Rodriguez says. And brands, including Wegovy and Ozempic, often cost around $1,000 per month out of pocket. In general, insurers wont cover the drug for prediabetes either.Although Rodriguez and her colleagues didnt look directly at insurance coverage in the new study, they did find that people with higher incomes were more likely to stick with the medication. They also found that people who struggled with gastrointestinal side effects were more likely to quit. But for many who stopped, it wasnt necessarily a permanent decision; about a third of those without type 2 diabetes restarted the drug within a year, often after they regained weight. Researchers havent investigated the effects of stopping and restarting the drug.Why someone would stop and restart these medications is a nuanced question. It could be a mix of renewed access, changes in insurance coverage and medical factors. Peoples perceptions of weight and obesity likely play a strong role, too. Sometimes [GLP-1 medications] are painted as a cosmetic drug, and obesity [is presented] as a cosmetic problem, Khan says. I think that stigma creates problems, for both patients and clinicians.
