Childhood obesity is one of the most alarming health problems of the 21st century, and it is much more than an aesthetic or overweight problem, with serious implications both in childhood and in adulthood, as it is associated with a significantly increased risk of developing chronic diseases such as type 2 diabetes, hypertension and cardiovascular problems. According to the World Health Organization (WHO), the number of overweight or obese children in the world has reached epidemic proportions, with more than 390 million children aged 5 to 19 affected. Despite global efforts to slow its advance, therapeutic tools aimed at the youngest children are limited. Currently, there are no approved drugs for the treatment of non-monogenic and non-syndromic obesity in children under 12 years of age. However, a recent study sheds light on the potential of liraglutide, a drug that has proven effective in adults and adolescents, to combat obesity in children between 6 and 12 years of age.
Treatment for childhood obesity has traditionally been based on lifestyle changes: balanced diet, physical activity and behavioural modifications. However, the response to these changes may be insufficient for some children, and this is where drugs come into play. Although liraglutide has been approved for the treatment of obesity in adolescents and adults, its efficacy and safety in the paediatric population had not yet been proven. A recent phase 3a clinical trial seeks to change this situation. The study was presented at the annual meeting of the European Association for the Study of Diabetes (EASD) in Madrid, held from 9 to 13 September, and its results have been published in the New England Journal of Medicine. They show that children aged 6 to 12 years who took liraglutide for just over a year experienced a 7.4% reduction in BMI compared to placebo and experienced improvements in blood pressure and blood sugar control.
A clinical trial with promising results for childhood obesity
Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It mimics the action of a hormone called GLP-1 to reduce appetite and feelings of hunger, slow the release of food from the stomach, and increase feelings of fullness after eating and is administered daily, as an injection.
The phase 3 trial, which was funded by Saxenda (liraglutide) manufacturer Novo Nordisk and was conducted over 56 weeks with an additional 26 weeks of follow-up, evaluated the efficacy of liraglutide in 82 obese children (53.7% boys) aged 6 to 12 years. At baseline, the average age was 10 years, BMI was 31.0 kg/m2, and body weight was 70.2 kg. 54.9% of children had at least one obesity-related complication, such as insulin resistance or precocious puberty. Participants were randomly assigned in a 2:1 ratio to receive either a daily subcutaneous dose of liraglutide 3.0 mg (or the maximum tolerated dose) or a placebo injection. All participants received individualized counseling at each visit to encourage adherence to a healthy diet and regular physical activity (with a goal of 60 minutes per day of moderate- to high-intensity exercise).
Children of this age are constantly growing, so body weight would be expected to increase over the course of a year. The primary endpoint was percentage change in body mass index (BMI), a metric that takes into account height as well as weight and is therefore more informative for assessing overweight and obesity, the researchers note. The results were compelling: children treated with liraglutide showed an average 5.8% reduction in their BMI, compared with a 1.6% increase in the placebo group. This represents a difference of 7.4 percentage points between the two groups, a statistically and clinically significant figure.
In addition, other notable improvements were observed: body weight decreased by an average of 1.6% in the liraglutide group, while in the placebo group it increased by 10%. In addition, 46% of children who received liraglutide experienced a reduction of at least 5% in their BMI, compared to only 9% in the placebo group. These results are encouraging, as they show that the drug can be an effective tool for reducing weight in children with obesity.
Lead author Professor Claudia Fox, from the Center for Pediatric Obesity Medicine at the University of Minnesota Medical School, said: “Although there is no consensus on the definition of a clinically significant reduction in BMI in children, a 5% reduction has previously been shown to be associated with an improvement in some obesity-related health conditions. In our study, diastolic blood pressure and haemoglobin A1c [HbA1c]a measure of blood sugar control, improved more in children who received liraglutide than in those who received placebo.”
Safety and adverse effects: an aspect to consider in slimming drugs
One of the critical issues when considering any drug treatment in children is safety. The trial reported that 89.3% of children receiving liraglutide experienced some type of adverse event, compared to 88.5% of those taking placebo. Most of these events were mild to moderate, and gastrointestinal side effects, such as nausea, vomiting and diarrhea, were more common in the liraglutide group (80.4% vs. 53.8%).
However, serious adverse events were also reported in 12.5% of participants treated with liraglutide, compared with 7.7% in the placebo group. Four of the seven serious adverse events in the liraglutide group were gastrointestinal in nature and 10.7% of patients in the liraglutide group discontinued treatment due to side effects, compared with none in the placebo group. Although these figures may seem worrying, it is important to stress that the potential benefits of treatment, in terms of reducing BMI and the associated risk of obesity, could outweigh the risks, provided the drug is administered under strict medical supervision. BMI and body weight increased in both groups after treatment was stopped.
“Liraglutide is a less effective drug than others currently used for weight loss in adults, but was presumably chosen for study by these researchers because it has been used for many years and has a well-established safety record,” Stephen O’Rahilly, Professor of Clinical Biochemistry and Medicine and Director of the Wellcome-MRC Institute of Metabolic Sciences-Metabolic Research Laboratories at the University of Cambridge, told SMC.
Implications for the future of childhood obesity treatment
This trial represents a promising first step towards liraglutide being approved as a treatment for obesity in children under 12 years of age, an age group that has so far been neglected in this field. While the results are encouraging, further long-term studies are crucial to assess the drug’s sustained effects and safety as children grow older.
Liraglutide could become a valuable tool in the fight against childhood obesity, provided it is used as part of a comprehensive approach that includes lifestyle changes. Such multidimensional interventions are essential to address the complexity of obesity, a disease that affects not only the body, but also the mind and social environment of the child.
As research progresses, the hope is that more safe and effective therapeutic options will emerge to treat children with obesity, allowing them to lead healthier and fuller lives. In the meantime, prevention remains the key: a balanced diet, regular physical activity and an environment that encourages healthy habits from childhood are the fundamental pillars to combat this global epidemic.
This trial opens up new possibilities, but also raises questions about the balance between risk and benefit in using drugs to treat childhood obesity. Answers will come with time and further studies, but what is clear is that liraglutide represents a new tool in the fight against one of the greatest challenges of modern public health.
