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Liraglutide (Saxenda) added to lifestyle intervention helped reduce BMI in young children with obesity, the phase IIIa SCALE Kids trial found.

By week 56, kids, ages 6 to <12 years, on once-daily 3-mg 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 in Minneapolis, and colleagues in the .

"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 kids on liraglutide compared with -0.3 for kids 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," stated Timothy Barrett, MB, PhD, of the University of Birmingham, and Julian Hamilton‑Shield, MD, of the University of Bristol, both in 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 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 than the 0.22 difference reported in the SCALE Teens trial in adolescents 12 to 17, which underpinned FDA approval for that age group in 2020. Prior to 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%) had early puberty as a result of their obesity, most likely."

While none had T2D, 20% had insulin resistance.

Kicking off with a 2-week screening period followed by a 12-week run-in period, 56 kids were randomized 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 0.6 mg/day for 1 week for participants with a body weight at randomization of at least 45 kg (0.3 mg per day for 1 week for those with a body weight at randomization of <45 kg). It was increased in increments of 0.6 mg/week over a maximum of 8 weeks (for participants with a body weight of ≥45 kg) or 10 weeks (for those with a body weight <45 kg) until a once-daily dose of 3.0 mg or the maximum tolerated dose was reached.

Lifestyle interventions consisted of counseling 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 favored liraglutide:

• BMI reduction ≥10%: 35% vs 4% with placebo
• Waist circumference change: -2 cm vs 1.3 cm
• Change in systolic blood pressure (BP): -1.7 mm Hg vs 1.7 mm Hg
• Change in diastolic BP: -1.2 mm Hg vs 3.0 mm 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 diarrhea 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 observed; however, the time range was not sufficient to determine long-term effects," Barrett and Hamilton‑Shield commented.

To help answer these lingering questions, Fox said the 3-year, open-label extension phase of the trial is still ongoing and is 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 2 years of off-treatment [with] observation," she said. "The goal is to get further longer-term data on safety and efficacy."