There is a need for comprehensive data on the long-term effects of weight loss drugs such as semaglutide or tirzapatide, as well as strategies for maintaining a healthier weight once people stop using them, argues a multidisciplinary team led by researchers from UCL.
In an editorial published in Nutrition Bulletin, the group of obesity management professionals acknowledge the promise of the new generation of weight loss drugs to change the management of obesity and allow more people to achieve their health goals. But they also caution that a multidisciplinary approach, which may include psychological, surgical and dietetic support, should be taken to avoid unintended issues and ensure patient safety.
Glucagon like peptide-1 receptor agonists (GLP-1 RAs) were originally developed as a type-2 diabetes treatment. The best known GLP-1 RA for obesity management, semaglutide, is the active ingredient in the drugs Wegovy and Ozempic. Wegovy was first licensed specifically for obesity management in the US in 2021 and in the UK in 2024.
These drugs have gained widespread media attention as potentially 'simple solutions' to the complex, relapsing, chronic condition that is obesity, due to their ability to 'turn off' hunger and their success in helping people to shed weight.
Dr Adrian Brown, a dietitian and lead author of the editorial from UCL Division of Medicine, said: "Given the increasing number of people living with obesity worldwide, we should be open to all available treatments and GLP-1 RAs are certainly a welcome addition to the tools we have available to manage obesity. In terms of their ability to help patients physically lower their weight, they are unmatched by other tools at our disposal apart from bariatric/metabolic surgery.
"But there are some key considerations healthcare professionals need to be mindful of when prescribing these medications. At present there are some unknowns related to their use in clinical practice alongside challenges in access. There remains uncertainty about how best to deliver optimal multidisciplinary services to support the effective use of GLP-1 RAs, particularly in the long term. These drugs need to be part of a multimodal approach to obesity management and not seen as a panacea."
A multidisciplinary team (MDT) approach to weight management will typically involve lifestyle, behavioural and psychological support, to help individuals reflect on their relationship with food and the nutritional profile of what they eat, as well as physical therapy. It may also involve treatments like bariatric surgery, which is designed to make the stomach smaller, alter appetite hormone and reduce the amount of food eaten. But bariatric/metabolic surgery would always be accompanied by MDT support to help the individual eat a balanced, healthy diet and avoid possible complications.
Dr Brown said: "Anyone who has tried to lose weight through a calorie-deficit diet and physical activity will attest that this is a long, slow process requiring a huge amount of work and self-discipline. In this light, the ability of GLP-1 RAs to 'turn off' hunger, addressing the underlying biology of obesity, and make people feel full is incredibly powerful and it would be easy to see them as a simple solution.
"Those using GLP-1 RAs will typically eat a lot less, which carries potential risks. It can result in individuals struggling to consume enough protein and micronutrients, for example, or exacerbating existing nutritional deficiencies that may not have been checked for."
The authors also point to a lack of comprehensive data on loss of muscle mass resulting from use of GLP-1 RAs. In two trials, STEP1 and SUTAIN, around two fifths of the weight lost by participants was lean tissue, but it remains unclear whether this would reduce physical function.
From a psychological perspective, the authors say that the 'psychosocial' aspect of GLP-1RA use is underexplored. There are higher levels of psychiatric or psychological issues among people seeking obesity management treatment.
Dr Emma Shuttlewood, a clinical psychologist and author of the editorial from University Hospitals Coventry and Warwickshire NHS Trust, said: "We know that many people who struggle with obesity seek reward or pleasure in energy-rich foods. If this reward pathway is removed, there may be a higher risk of using unhealthy sources, such as alcohol or overspending, to meet their emotional needs as observed in some patients who've had bariatric surgery.
"The dampening of reward centres may also lead to depression, self-harm and suicide. I think much clearer guidance is required for all professionals working with patients undergoing GLP-1 RA therapy to understand the possible impact on psychological wellbeing in the longer term."
Dr Brown concluded: "There's no denying that GLP-1 RAs have the potential to permanently change the management of obesity and enable more individuals to achieve their health goals, which is fantastic news for the millions of people living with obesity.
"What we need now is for clinical service providers and commissioners to come together to figure out how to best deliver multidisciplinary care that will enable patients to improve their health and wellbeing safely and sustainably."
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