BMJ analysis raises questions about long-term use of GLP-1 RA therapies without sustained lifestyle support.
Stopping pharmacological weight-loss treatment is associated with rapid weight regain and loss of previously achieved cardiometabolic benefits, according to a major analysis published in the BMJ.
Researchers from the University of Oxford found that patients regained an average of 0.4 kg per month after stopping weight-loss drugs, with modelling suggesting that all weight lost is likely to be regained within 1.7 years.
Improvements in cardiometabolic risk markers, including blood pressure, cholesterol and markers of diabetes risk, were projected to return to pre-treatment levels within 14 months of discontinuation.
Weight regain occurred almost four times faster after stopping pharmacological treatment than after stopping behavioural weight-loss programs based on diet and physical activity, regardless of the amount of weight initially lost.
The findings raise important considerations for GPs as use of GLP-1 receptor agonists continues to rise in primary care.
“From a behavioural science perspective, this review highlights a key limitation of relying on weight management medications as a stand-alone strategy,” said Associate Professor Dominika Kwasnicka, a behavioural scientist and public health researcher at the University of Melbourne.
“While the projected return to baseline weight and cardiometabolic risk is based on modelling rather than long-term observed data, the underlying pattern is consistent across studies and analyses.”
While weight management medications can be highly effective during use, Professor Kwasnicka noted that obesity is a chronic condition shaped by behaviours, environments and ongoing support.
“Medications primarily act on biological pathways and do not, on their own, establish the behavioural or systemic changes needed to sustain weight loss over time,” she said.
She said the findings also had “important policy implications” for Australia.
“Access to these medications is expanding, often with substantial out-of-pocket costs and limited structured follow-up,” said Professor Kwasnicka.
“Without long-term planning, there is a risk of short-term benefit followed by weight regain and loss of health gains once treatment ceases.
“These results support the need to embed pharmacotherapy within comprehensive, long-term models of care that include behavioural support, continuity of care, and realistic discussions about duration of treatment, rather than viewing these medications as short-term solutions.”
Highly effective weight-management medications, particularly GLP-1 RAs such as semaglutide and tirzepatide, have transformed obesity care by enabling substantial weight loss and short-term improvements in metabolic health.
However, real-world evidence suggests that around half of patients discontinue GLP-1 RA therapy within 12 months, often due to cost, tolerability or expectations that treatment will be short term, making it important to understand the consequences of stopping therapy.
The analysis included 37 randomised and observational studies published up to February 2025, involving 9341 adults.
The studies compared weight-loss medications with placebo or non-drug behavioural interventions. Average treatment duration was 39 weeks, with a mean follow-up of 32 weeks after treatment cessation.
While only eight studies included newer GLP-1 agents and follow-up beyond 12 months was limited, three different analytical approaches produced consistent results, strengthening confidence in the findings.
The authors concluded that the evidence cautions against short-term use of weight-management medications and highlights the need for cost-effective strategies to support long-term weight control.
They emphasised that pharmacotherapy alone is unlikely to be sufficient for sustained benefit and that primary prevention remains critical.
“As obesity is a chronic and relapsing condition, prolonged treatment with WMM [weight management medications] may be required to sustain the health benefits,” the researchers wrote.
“One trial did show successful weight loss maintenance over four years with continuous semaglutide treatment. In the USA and Denmark, early evidence shows that discontinuation rates outside of clinical trials are around 50% at one year.
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“This evidence suggests that despite their success in achieving initial weight loss, these drugs alone may not be sufficient for long term weight control. Further research is needed to study how to support people to use these drugs effectively, either through prolonged adherence or, possibly, through intermittent periods of treatment.”
In a linked editorial published in the BMJ, US researcher Associate Professor Qi Sun, of the Channing Division of Network Medicine at the Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, wrote that the findings cast doubt on the idea that GLP-1 receptor agonists represent a definitive cure for obesity.
He argued that patients should be made aware of the high rates of treatment discontinuation and the metabolic consequences of stopping therapy, and that healthy dietary and lifestyle practices should remain the foundation of obesity management, with medications used as adjuncts rather than replacements.
“This is a timely investigation because, as the authors pointed out, real world observations suggested that a large proportion of people would discontinue use of a GLP-1 receptor agonist within 12 months of initiation,” Professor Sun wrote.
“The results are not surprising given that it is well-documented that reduced adherence to, or cessation of, dietary and lifestyle interventions leads to similar patterns of weight regain. Nevertheless, the study findings casted doubt on the notion that GLP-1 receptor agonists are a perfect cure for obesity.
“Issues such as high costs, side effects, and the inconvenience of injections are among some common reasons for discontinuing the medications.”
He suggested one strategy was to switch to healthy diets and healthy lifestyles that have been robustly and consistently proven to be effective in preventing excess weight regain in observational studies with extended follow-up, “although further research is needed to study weight regain in individuals who adopt a heathier lifestyle after the cessation of GLP-1 receptor agonists”.
Professor Sun said the benefits of managing and treating obesity with dietary and lifestyle practices go beyond weight control and can lead to numerous additional health benefits.
He warned that GLP-1 RAs “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-1 receptor agonists should be aware of the high discontinuation rate and the consequences of cessation of medications,” he wrote.
“Effective public health measures, such as taxation on sugary beverages, clear food labelling, and subsidies for fresh fruit and vegetables, should be in place to facilitate the adherence and improvement of diet quality,” he said.
Professor John B Dixon from the Iverson Health Innovation Research Institute at Swinburne University of Technology, Melbourne, agreed.
“This analysis by an excellent UK team shows the data we have all been aware of for years,” he said.
“The new obesity management medications have greatly improved efficacy, but do not cure the disease of disordered energy balance.
“All new medications are expensive initially, and with time and competition, become more cost-effective.
“False dichotomies dominate much of the thinking: prevent vs treat, behavioural change vs medical/surgical therapy, and there are so many more. You can see them emerging in this review.”
