People return to their baseline weight and lose all cardiometabolic benefits in less than 2 years after stopping semaglutide or tirzepatide, a new meta-analysis found.

“Real-world observations estimate that 50% of people with obesity discontinue GLP-1 receptor agonists within 12 months of initiation, so it is important to characterize what happens to body weight after cessation of treatment,” Sam West, postdoctoral researcher at the Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, England, and colleagues wrote in their paper, published on January 7, 2026, in The BMJ.

The data, from 9341 participants in 37 studies of all types of weight-loss medications including older ones, showed that the return to baseline weight occurred in an average of 1.7 years overall. The average monthly regain was 0.4 kg, about four times faster than after behavioral interventions regardless of the amount of weight initially lost. Cardiometabolic benefits were projected to return to baseline even sooner after stopping GLP-1s.

“These drugs [GLP-1s] are highly effective and a valuable tool in obesity treatment. But obesity is a chronic relapsing condition. It’s very clear that some type of treatment or intervention needs to continue if we’re going to sustain the benefits of these treatments,” the study co-author Susan Jebb, PhD, OBE, professor of diet and population health in the same institution as West, said during a Science Media Centre press briefing.

Jebb continued, “I think it’s important that these drugs are considered as one option within the wider obesity treatment portfolio. This is not the only way to treat obesity. We need to ensure we’re selecting the right treatment for the right patient at the right time if we want to maximize the cost-effectiveness to the [UK’s National Health Service (NHS)]. That’s important because of the incredibly large numbers of people who could benefit from treatment.”

In an accompanying editorial, Qi Sun, MD, associate professor of medicine at Brigham and Women’s Hospital and Harvard Medical School in Boston, wrote, “GLP-1 receptor agonists should not be relied on as a magic cure for treating obesity. While considerable weight loss, even if temporary, may still bring some health benefits for those with obesity, people using [GLP-1s] should be aware of the high discontinuation rate and the consequences of cessation of medications. Healthy dietary and lifestyle practises should remain the foundation for obesity treatment and management, with medications such as [GLP-1s] used as adjuncts. Such practises not only help prevent excess weight gain but can also lead to numerous health benefits that go beyond weight control.”

This study emphasizes that weight regain is “amplified” when patients stop taking the drugs, said Adam Collins, PhD, University of Surrey, Surrey, England, and maintaining the weight loss can be a challenge.

Providing GLP-1 artificially higher than normal may cause patients to produce less GLP-1 naturally. “No problem when taking the drugs, but as soon as you withdraw this GLP-1 ‘fix,’ appetite is no longer kept in check, and overeating is far more likely. Like any addict, going cold turkey is a real challenge. This is further exacerbated if the individual in question has relied solely on GLP-1 to do the heavy lifting during weight loss, ie, artificially suppressing their appetite without them establishing any dietary or behavioral changes that would help them in the long run,” Collins added.

What Happens When Weight-Loss Medications Are Stopped?

In the included studies, all medications were given for 8 weeks or longer, with follow-up for at least 4 weeks, in adults with overweight or obesity. There were 6322 participants receiving the intervention and 3019 control participants. Average treatment duration was 10 months, and the follow-up was 8 months.

Participants lost an average of 8.3 kg during treatment but regained 4.8 kg after 1 year, at an average rate of 0.4 kg/mo. They returned to baseline weight by 1.7 years after the treatment was stopped.

In a separate subset analysis of 1776 participants in six studies of semaglutide and tirzepatide, the average weight loss was 14.7 kg, regain was 9.9 kg at a rate of 0.8 kg/mo, with a projected return to baseline at 1.5 years. (Results were projected because results for semaglutide and tirzepatide were only available up to 1 year.)

All cardiometabolic outcomes measured — including A1c, fasting glucose, systolic and diastolic blood pressure, total cholesterol, and triglycerides — were also projected to return to baseline within 1.4 years after stopping the medications. 

By comparison, a previous study from the same group on weight regain after behavioral weight-loss programs showed less weight loss, 5.1 kg, but also much slower weight regain, 0.1 kg/mo, and much longer return to baseline, 3.9 years. “Greater weight loss tends to result in faster weight regain, but it is consistently faster after medication regardless of the amount of weight loss in the first place,” West noted during his presentation of the data at the briefing.

Provision of behavioral support during treatment with incretin mimetics resulted in an extra 4.6 kg of weight loss. However, there was no evidence that the rate of weight regain differed with or without behavioral support, during or after treatment, West reported.

Can the Medications Be Cost-Effective for the NHS?

The UK’s National Institute for Health and Care Excellence considers an intervention cost-effective at a threshold of £20,000 and £30,000 per additional quality-adjusted life-year (QALY) gained. Thus, it does consider incretins to be cost-effective for certain groups of people: those with BMI ≥ 35 and one comorbidity with a model assuming weight regain at 1 year for tirzepatide (£21,372) and those with BMI 30-35 and health risks or BMI ≥ 35 for semaglutide (£21,060) with weight regain at 2 years.

However, these new findings suggest that weight regain may be quicker, which could change the cost-effectiveness calculation, noted co-author Dimitrios A. Koutoukidis, PhD, also of Oxford.

He noted that the NHS is currently rolling out treatment based on clinical need, prioritizing people with higher BMI and/or more comorbidities, which would likely improve cost-effectiveness. Other weight-loss interventions also could be more cost-effective, including dietary behavioral programs for people who don’t qualify for medications based on NHS criteria (~£2394/QALY) or bariatric surgery for those with severe/complex obesity (~£7129/QALY).

Jebb pointed out, “because these are new drugs, and not many of the clinical trials continued to study people after the medication ends, the data on what happens later on are quite limited. So I think it’s incredibly important, as more and more people take these drugs, that we take the opportunity to look at the real-world data as it emerges, and have a look at what happens in the longer term. This is a kind of an early look, I would say.”

This project was funded in part by the National Institute for Health and Care Research (NIHR) Oxford Biomedical Research Centre. Jebb reported being supported by the NIHR Oxford Biomedical Research Centre, NIHR Oxford Health Biomedical Research Centre, and NIHR Applied Research Collaboration Oxford and Thames Valley. Koutoukidis also reported being supported by an NIHR advanced fellowship. Jebb reported being in receipt of, and West reported being partially funded by, a research grant from the Novo Nordisk Foundation. Collins declared having no conflicts.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape Medical News, with other work appearing in The Washington Post, NPR’s Shots blog, and diaTribe. She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social.