Liraglutide Reduces BMI by Almost 6% in Children Aged 6-12

The glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide is the first in its class to show benefits in young children with obesity, according to results from the phase 3a SCALE-KIDS trial presented at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting and simultaneously published in The New England Journal of Medicine.
After a year of treatment, children who received daily liraglutide injections had a 5.8% reduction in body mass index (BMI), while those receiving placebo experienced a 1.6% increase in BMI. Almost half of the children who received liraglutide had at least a 5% reduction in BMI. 
Body fat was not directly measured in the trial, but children taking liraglutide also had small improvements in diastolic blood pressure and A1c.
The authors acknowledge there is no consensus on what constitutes a clinically meaningful change in BMI in children but note that 5% reduction has been associated with improvement in obesity-related health conditions.
BMI corresponds “quite well” with percentage body fat in children with severe obesity, lead author Claudia Fox, MD, MPH, codirector of the Center for Pediatric Obesity Medicine at the University of Minnesota Medical School, told Medscape Medical News.
“I am very confident that this BMI reduction likely translates into significant reduction in body fat mass,” said Fox, who is also associate professor at the school’s division of pediatric gastroenterology, hepatology, and nutrition.
However, because body composition was not measured, “the possibility of a loss of muscle mass, at least initially, cannot be excluded,” write Timothy Barrett, MBBS, PhD, and Julian Hamilton-Shield, MBChB, MD, of the College of Medicine and Health at the University of Birmingham and Bristol Medical School at the University of Bristol, UK, in an accompanying editorial.
Barrett and Hamilton-Shield further disagree with Fox, noting: “We know that BMI is a poor surrogate for fat mass.” 
Even so, the editorialists acknowledge that “the reduction in the BMI standard-deviation score of 0.7 in the liraglutide group” in the trial “is likely to improve metabolic variables such as insulin sensitivity and hepatic steatosis.”
The US Food and Drug Administration (FDA) approved liraglutide in 2020 for teens aged 12-17. The FDA approved the GLP-1 agonist semaglutide (Wegovy, Novo Nordisk) in 2023 for the same age group. However, no GLP-1 agonist has been approved for children under age 12. 
Liraglutide could offer a new tool for younger children, said Fox. “Kids who have severe forms of obesity are desperate for intervention,” she said, noting that for many, more exercise and changing diet are not the answer. 
Fox said she has had patients with fatty liver disease and hypertension at age 9 and had a 10-year-old with a suicide attempt because of bullying. 
Trial Details 
Of a total of 82 children, 56 were randomized to liraglutide and 26 to placebo. Children who weighed more than 45 kg were started on liraglutide 0.6 mg/day for the first week, increasing by 0.6 mg per week over a maximum of 8 weeks until they reached a once-daily dose of 3 mg. Those who weighed less than 45 kg received a starting dose of 0.3 mg, escalating over 10 weeks in increments of 0.6 mg up to the maximum 3-mg dose.
At the trial end, those receiving liraglutide had a 1.6% increase in body weight, compared with a 10% increase in the placebo group. 
In addition, those taking liraglutide had reductions in systolic and diastolic blood pressure of 1.7 mm Hg and 1.2-mm Hg, respectively, and about a 0.2% decrease in A1c, Fox reported.
However, she urged caution when interpreting these results, noting that at baseline, the children didn’t have hypertension and that the change in A1c was negligible. 
Susma Shanti Vaidya, MD, MPH, a pediatric bariatric medicine specialist at Children’s National Hospital in Washington, DC, who was not involved with the study, said the weight gain was not alarming. 
“Overall, there was a slight increase in the weight, but they’re young kids and their linear growth outpaced that, which resulted in the BMI reduction,” she told Medscape Medical News.
The “improvement in cardiometabolic parameters” is exciting, she added.
As has been seen in trials of GLP-1 agonists in teens and adults, gastrointestinal side effects were common in the trial. 
Forty-five of the 56 (80%) children who received liraglutide had gastrointestinal adverse events, which occurred mainly during the dose-escalation phase of the study, said Fox. Three serious adverse events thought to be drug-related included two cases of vomiting and one of colitis. Six liraglutide recipients (11%) discontinued the drug because of side effects.
Interestingly, 14 of 26 (54%) placebo recipients also reported GI symptoms, Fox added.
Daily Injections a Hurdle?
Both Fox and Vaidya noted that daily injections could be challenging for children, especially the youngest. 
However, the injector pen needles are fairly small and many patients overcome concerns about the injections somewhat quickly, said Vaidya. 
Fox said she initially thought it would be difficult to get parents and children to participate in the study because of the injections, but “we had to turn people away.” 
“There’s a huge, huge need out there,” she said.
Vaidya agreed. “I have many patients who are less than 12 years of age who really need some other pharmacotherapeutic option,” she said.
“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,” write Barrett and Hamilton-Shield.
Both clinicians said that rapid uptake of the therapy is not likely, as insurers won’t cover the drug unless it has an FDA-approved indication.
Novo Nordisk told Medscape Medical News that, based on the study findings, it has submitted an application to the FDA for approval for liraglutide for children aged 6 to < 12 years living with obesity.
The study was funded by Novo Nordisk. Fox has disclosed being an investigator for Eli Lilly and Novo Nordisk but does not receive fees or honoraria. Vaidya has reported no relevant financial relationships.
Alicia Ault is a Saint Petersburg, Florida-based freelance journalist whose work has appeared in publications including JAMA and Smithsonian.com. You can find her on X @aliciaault. 
 
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