Researchers say that liraglutide (Saxenda), in combination with lifestyle intervention, helped reduce the body mass index (BMI) in obese children as young as six.
In the Novo-Nordisk-funded phase IIIa SCALE Kids trial, by week 56, children between six and 12, on once-daily 3mg liraglutide, lost 5.8% of BMI compared with a 1.6% gain with lifestyle intervention alone (estimated difference -7.4%, 95% CI -11.6 to -3.2), reported Claudia Fox, MD, of the University of Minnesota Medical School, and colleagues in the New England Journal of Medicine.
“The backbone of treatment – lifestyle therapy – is often insufficient in achieving clinically significant and durable BMI reduction,” Fox said at the European Association for the Study of Diabetes (EASD) annual meeting in Madrid, where the findings were simultaneously presented. “There are no medications that are approved for the treatment of obesity in this age population, except for the rare forms of monogenic or syndromic obesity.”
Nearly half (46%) of the liraglutide group versus 9% of the placebo group lost at least 5% of BMI (adjusted OR 6.3, 95% CI 1.4-28.8).
Average body weight change was 1.6% with liraglutide and 10% with placebo. Mean change in BMI standard-deviation score was -0.7 for children on liraglutide compared with -0.3 for their peers on lifestyle intervention alone (difference -0.4, 95% -0.6 to -0.2).
“The results 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,” said Timothy Barrett, MB, PhD, of the University of Birmingham, and Julian Hamilton‑Shield, MD, of the University of Bristol, England.
While there is still a possibility of a loss of muscle mass – at least initially – since body composition wasn’t measured, Barrett and Hamilton-Shield said in an accompanying editorial that the magnitude of the reduction in the BMI standard-deviation score “exceeds this threshold and is likely to improve metabolic variables such as insulin sensitivity and hepatic steatosis”.
This BMI standard-deviation score treatment difference was nearly double the 0.22 difference reported in the SCALE Teens trial in adolescents aged 12 to 17, which underpinned FDA approval for that age group in 2020.
Before approval for teens, the GLP-1 receptor agonist was approved for chronic weight management in adults in 2014 and at a lower dose (Victoza) for type 2 diabetes (T2D) in 2010.
SCALE Kids was a 23-site, nine-country trial that enrolled children with a BMI in the 95th percentile or higher in a 2:1 ratio. Average age was 10 years, 54% were male, and 72% were white. All had to have failed at losing sufficient weight with lifestyle interventions.
At baseline, average BMI was 31 and most had class 2 (37%) or class 3 obesity (39%). “These children had very severe forms of obesity,” Fox said. “A fair amount (12%) were likely to have had early puberty as a result of their obesity.” While none had T2D, 20% had insulin resistance.
Kicking off with a two-week screening period followed by a 12-week run-in period, 56 children were randomised to the liraglutide group and 26 to placebo. This was followed by a 56-week treatment period and 26-week off-treatment period.
Fox pointed out this was a much smaller sample size than adult trials of similar agents. “With such a small sample, it’s hard to know if there are rare side effects that … will emerge once the numbers of exposure are higher.”
Liraglutide was started at a dose of 0.6mg/day for one week for participants with a body weight at randomisation of at least 45kg (0.3mg per day for one week for those with a body weight at randomisation of <45kg).
It was upped in increments of 0.6mg/week over a maximum of eight weeks (for participants with a body weight of ≥45kg) or 10 weeks (for those with a body weight <45kg) until a once-daily dose of 3.0mg or the maximum tolerated dose was reached.
Lifestyle interventions consisted of counselling by a healthcare professional encouraging a healthy diet, and a goal of 60 minutes per day of moderate-to-high intensity physical activity, with an optional activity tracker provided.
Several other secondary endpoints also significantly favoured liraglutide:
• BMI reduction ≥10%: 35% vs 4% with placebo
• Waist circumference change: -2cm vs 1.3cm
• Change in systolic blood pressure (BP): -1.7mm Hg vs 1.7mm Hg
• Change in diastolic BP: -1.2mm Hg vs 3.0mm Hg
• Change in HbA1c: -0.2% vs -0.1%
As expected with a GLP-1 agent, gastrointestinal adverse events (AEs) were more common in the liraglutide group (80% vs 54%). A total of 11% of the liraglutide group discontinued treatment due to AEs (5% of which was GI-related). Nausea, vomiting, and diarrhoea were the most common AEs; three cases of vomiting were deemed serious and required emergency care.
“It is important to note for this age group that no identified effects on growth and puberty were observedm however, the time range was not sufficient to determine long-term effects,” Barrett and Hamilton‑Shield commented.
Fox said the three-year, open-label extension phase of the trial is ongoing and expected to wrap in January 2027.
“At the end of the 26 weeks of off-treatment, eligible participants were asked if they wanted to restart the medication again for an additional 56 weeks and this was followed by an additional two years of off-treatment (with) observation,” she said.
“The goal is to get further longer-term data on safety and efficacy.”
Study details
Liraglutide for children 6 to <12 years of age with obesity – a randomised trial
Claudia Fox, Margarita Barrientos-Pérez, Silva Arslanian et al.
Published in NEJM on 10 September 2024
Abstract
Background
No medications are currently approved for the treatment of nonmonogenic, nonsyndromic obesity in children younger than 12 years of age. Although the use of liraglutide has been shown to induce weight loss in adults and adolescents with obesity, its safety and efficacy have not been established in children.
Method
In this phase 3a trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we randomly assigned children (6 to <12 years of age) with obesity, in a 2:1 ratio, to receive either once-daily subcutaneous liraglutide at a dose of 3.0 mg (or the maximum tolerated dose) or placebo, plus lifestyle interventions. The primary end point was the percentage change in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters). The confirmatory secondary end points were the percentage change in body weight and a reduction in BMI of at least 5%.
Results
A total of 82 participants underwent randomisation; 56 were assigned to the liraglutide group and 26 to the placebo group. At week 56, the mean percentage change from baseline in BMI was −5.8% with liraglutide and 1.6% with placebo, representing an estimated difference of −7.4 percentage points (95% confidence interval [CI], −11.6 to −3.2; P<0.001). The mean percentage change in body weight was 1.6% with liraglutide and 10.0% with placebo, representing an estimated difference of −8.4 percentage points (95% CI, −13.4 to −3.3; P=0.001), and a reduction in BMI of at least 5% occurred in 46% of participants in the liraglutide group and in 9% of participants in the placebo group (adjusted odds ratio, 6.3 [95% CI, 1.4 to 28.8]; P=0.02). Adverse events occurred in 89% and 88% of participants in the liraglutide and placebo groups, respectively. Gastrointestinal adverse events were more common in the liraglutide group (80% vs. 54%); serious adverse events were reported in 12% and 8% of participants in the liraglutide and placebo groups, respectively.
Conclusions
Among children (6 to <12 years of age) with obesity, treatment with liraglutide for 56 weeks plus lifestyle interventions resulted in a greater reduction in BMI than placebo plus lifestyle interventions.
NEJM article – Liraglutide for children 6 to <12 with obesity – a randomised trial (Open access)
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