Liraglutide 3 mg reduces BMI for children with obesity aged 6 to 11 years
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Key takeaways:
- Children receiving once-daily liraglutide 3 mg had a 5.8% decrease in BMI at 56 weeks.
- Adverse events were similar to what was seen in adult and adolescent trials.
Children with obesity receiving once-daily liraglutide 3 mg had a greater reduction in BMI at 56 weeks than those receiving placebo, according to data presented at the European Association for the Study of Diabetes annual meeting.
As Healio previously reported, the FDA previously approved once-daily liraglutide (Saxenda, Novo Nordisk) and once-weekly semaglutide (Wegovy, Novo Nordisk) to treat obesity among adolescents aged 12 to 17 years. However, Claudia K. Fox, MD, MPH, associate professor in the division of pediatric gastroenterology, hepatology and nutrition, department of pediatrics; and co-director and fellowship program director for the center for pediatric obesity medicine at the University of Minnesota, noted there are no FDA-approved treatments for children with obesity. She presented findings from the phase 3a SCALE Kids randomized controlled trial, which were also simultaneously published in The New England Journal of Medicine.
“The goal of this study was to compare the effect, safety and tolerability of once-daily liraglutide 3 mg, as an adjunct to lifestyle therapy, on weight management in children aged 6 to less than 12 [years],” Fox said during a presentation.
Researchers enrolled 82 children aged 6 to 11 years with an age- and sex-adjusted BMI in the 95th percentile or higher without type 1 diabetes, without secondary causes of obesity and in Tanner stage 1 to 5 of puberty (54% boys; mean age, 10 years; 72% non-Hispanic white). Participants were randomly assigned 2:1 to once-daily 3 mg liraglutide or placebo for 56 weeks. All participants received lifestyle intervention. A 26-week off-treatment period followed the treatment portion of the study. The primary endpoint was percent change of BMI from baseline to 56 weeks. Confirmatory secondary endpoints were percent change in body weight at 56 weeks and the proportion of children with a BMI decline of at least 5% at 56 weeks.
Children receiving liraglutide had a 5.8% reduction in BMI at 56 weeks compared with a 1.6% BMI increase for the placebo group (estimated treatment difference, –7.4 percentage points; 95% CI, –11.6 to –3.2; P < .001). The liraglutide group had a 1.6% increase in body weight at 56 weeks vs. a 10% increase with placebo (estimated treatment difference, –8.4 percentage points; 95% CI, –13.4 to –3.3; P = .001). Of the participants, 46% receiving liraglutide had a BMI reduction of at least 5% at 56 weeks compared with 9% of the placebo group (adjusted OR = 6.3; 95% CI, 1.4-28.8).
Fox said percent change in BMI was used as the primary outcome to account for the growing height of children during the study.
“Children have the advantage of that they are continuing to grow in height,” Fox said during the presentation. “That really does impact our BMI much more so than looking at body weight alone.”
From baseline until the end of the off-treatment period at 82 weeks, the liraglutide group had a 0.8% BMI decrease compared with a 6.7% increase in BMI for the placebo group. Mean change in body weight from baseline to 82 weeks was a 10.7% increase with liraglutide and 19% increase with placebo.
Children receiving liraglutide had a 4.2 mm Hg greater decrease in diastolic blood pressure and a 0.1 percentage point larger decline in HbA1c at 56 weeks compared with the placebo group. There was no difference in systolic BP change between the two groups.
Adverse events occurred in 89% of the liraglutide group and 88% of the placebo group. A higher proportion of children receiving liraglutide reported gastrointestinal adverse events compared with placebo (80% vs. 54%), mostly due to a greater incidence of mild-to-moderate nausea and vomiting with liraglutide. Serious adverse events occurred in 12% of the liraglutide group and 8% of the placebo group. There were six children receiving liraglutide who discontinued treatment due to adverse events, of whom three discontinued due to gastrointestinal disorders. Fox said the observed gastrointestinal adverse events were similar to what was seen in adult and adolescent trials.
“This medication was generally well-tolerated in the pediatric population with no new safety concerns,” Fox said.
Open-label extension ongoing
In a related editorial published in NEJM, Timothy Barrett, MB, PhD, professor of pediatrics, honorary consultant in pediatric endocrinology and diabetes, and program director for the Wellcome Trust Clinical Research Facility at Birmingham Children’s Hospital and University of Birmingham in the U.K., and Julian HamiltonShield, MD, professor of diabetes and metabolic endocrinology at the University of Bristol and The Royal Hospital for Children in Bristol, U.K., discussed limitations of the trial. They noted body composition was not measured and described BMI as a “poor surrogate” for fat mass. They also discussed how BMI standard deviation scores increased during the off-treatment period, implying that continuous treatment with an obesity medication may be needed to maintain weight loss.
“Despite the need for further studies, the results of the trial reported by Fox et al. provide much needed evidence for the effects of a GLP-1 receptor agonist in young children with obesity, offering a therapeutic option in prepubertal children with severe obesity as an adjunct to healthy lifestyle interventions,” Barrett and Hamilton-Shield wrote.
Fox said an open-label extension phase of the study is currently ongoing. After the 26-week off-treatment period, participants from both the liraglutide and placebo groups can begin 56 weeks of open-label treatment with liraglutide. The treatment will be followed by annual safety follow-up visits for up to 2 years.
“This will provide us with much-needed longer-term safety and efficacy data in this younger population,” Fox said.
References:
Barrett T, et al. N Engl J Med. 2024;doi:10.1056/NEJMe2410560.
Fox CK, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2407379.
Perspective
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This study is truly a first of more to come in a very select group. At this time there is only one approved anti-obesity medication in children aged 6 to 11 years old. This lone medication is only for rare forms of obesity that are due to a single-gene mutation. Yet one in five U.S. children have obesity and most would not qualify for this medication. So essentially, we have no treatment for the vast majority of children struggling with obesity.
Liraglutide is an older GLP-1 receptor analog that is a once-daily subcutaneous injection that is relatively less effective than the newer once-weekly GLP-1 receptor agonists. The fact that the study showed significant weight loss and very acceptable safety will guide future studies with the more powerful once-weekly GLP-1 receptor agonists.
Obesity in childhood effects many aspects of growth and development. The deleterious medical effects such as fatty liver disease are well known, but the social and psychological effects can be just as damaging. Currently one of the fastest growing groups of all pediatric patients struggling with weight gain is the patient with serious obesity. Many health care providers are seeing these children on a daily basis (prevalence of 4% to 6%). To have a treatment option for this group would truly help with an unmet need.
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Fox CK, et al. LBA13. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 9-13, 2024; Madrid, Spain.
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