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A study published in the NEJM and being presented at the European Association for the Study of Diabetes Obesity looks at liraglutide in children.
Prof Stephen O’Rahilly FRS FMedSci, Professor of Clinical Biochemistry and Medicine and Director of the Wellcome-MRC Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, said:
“Drugs that target the GLP1 receptor, such as semaglutide and tirzepatide, are known to be effective and largely safe (though not without side effects) in the treatment of adults and adolescents living with obesity. Childhood obesity is an increasing problem and attempts to treat it through behavioural means are relatively ineffective. In this small but well-conducted study the authors report the results of a one year trial combining an older GLP1 receptor agonist, liraglutide, with diet and lifestyle advice and comparing outcomes in obese children aged 6 to 12 given the same advice and a placebo injection. Only 9% of children given the behavioural advice and placebo reduced their body mass index (BMI) by 5% or more over the year whereas 46% of the children treated with liraglutide achieved that reduction. More than a third of children treated with liraglutide reduced their BMI by 10% or more. Importantly, there were no adverse impacts of the drug on children’s growth or development. As is the case with adults, liraglutide treated children reported more nausea vomiting and diarrhoea than those treated with placebo but this could be managed by reducing the dose of the medication and gradually increasing it later, if necessary. Trends towards improvement in blood pressure and glucose metabolism in the liraglutide treated children suggest that they were likely to be obtaining health benefits from the reduction in the severity of their obesity.
“Liraglutide is a less effective drug than others now used for weight loss in adults but was presumably chosen for study by these investigators because it has been in use for many years and has a well-established safety record safety record. While efforts to prevent childhood obesity through altering the “obesogenic environment” remain a high priority, safe and effective treatments that can help obese children, particularly those where it is severe, are needed immediately. It seems likely that we see more trials in this age group, and that they will involve the use of increasingly more effective weight loss drugs.”
Dr Simon Cork, Senior Lecturer in Physiology, Anglia Ruskin University, said:
“Developing anti-obesity medication for use in children is complicated by the fact that children are actively growing, and therefore there is a possibility for greater risk, particularly with regards to appetite suppression, since such medication have the potential to stunt growth.
“Nevertheless, we know that people who experience obesity as a child are much more likely to be obese in adulthood, and experience the associated negative health outcomes that come with it. Therefore, the evidence that liraglutide is both safe and effective in children is positive. However, further studies over longer time periods will need to be undertaken to ensure that appetite suppression in these children does not have unforeseen negative consequences later in their development.”
Dr Nerys Astbury, Associate Professor – Diet & Obesity, Nuffield Department of Primary Health Care Sciences, University of Oxford, said:
“This paper published in the NEJM reports the findings of a phase 3a trial of liraglutide; an injectable GLP-1 agonist with current market approval for treatment of adults with type 2 diabetes and living with obesity in Europe and the USA.
“Childhood obesity is a strong predictor of adult obesity, which is associated with increased risk of developing many health conditions including type 2 diabetes, cardiovascular disease, liver and kidney diseases and several types of cancers which not only reduce patients’ quality of life but also responsible for substantial burden on healthcare budgets.
“There are no current licenced pharmacotherapies for childhood or adolescent obesity which are not related to genetic abnormalities or syndromes. Furthermore, there is limited evidence that any other weight management interventions are effective in treating obesity and overweight weight in children and adolescents.
“This study demonstrates that, using similar design to the previously published adult trials – participants aged 6-12 years were randomised to either an escalating dose of liraglutide (up to a maximum dose of 3mg) or a placebo with lifestyle advice received by both groups. After 56 weeks the mean change in body weight was -5.6% in the liraglutide group and -1.6% in the placebo (a difference of 7.4% favouring the liraglutide group).
“Children continue to grow – both height and weight continue to increase even in an individual who remains at the same BMI z score (percentile) relative to age and sex matched children (which may be considered similar to a weight stable adult). Therefore, assessing the impact of treatments to manage body weight is more complex in this group.
“The effects on change in body weight (%) in this study are not as marked as the effects reported in adults. There is also currently no consensus on what a clinically meaningful change in BMI in children and adolescence might look like, or other weight loss studies to compare this effect with.
“Furthermore, given the lack of effective interventions to date, any potential side effects of substantial weight loss related to growth are not known. Whilst all medications are associated with side effects, here the liraglutide group had more side effects – mainly related to mild-to-moderate gastrointestinal symptoms, and also severe side effects related to vomiting and colitis. Although there was no evidence that liraglutide detrimentally impacted changes in height, bone age or pubertal status, further longer-term follow-up of the participants and their growth patterns are required.
“These promising findings open up the possibility that at some time soon there will be safe and effective medications available for treating obesity in children and adolescents. Because treating children and adolescents living with obesity has the potential to have longer lasting health benefits, although these medications are currently costly, their value for reducing risk of conditions associated with obesity, and improving longer term health must be considered.”
‘Liraglutide for Children 6 to <12 Years of Age with Obesity — A Randomized Trial’ by Claudia K. Fox et al. was published in the New England Journal of Medicine at 23:01 UK time on Tuesday 10 September 2024.
DOI: 10.1056/NEJMoa2407379
Declared interests
Prof Stephen O’Rahilly: “SOR has provided consultancy services for numerous pharmaceutical companies but has not done so for Novo-Nordisk , the manufacturer of liraglutide, since 2017.”
Dr Simon Cork: “No CoI.”
Dr Nerys Astbury: “No conflicts.”