Liraglutide reduces BMI in younger children with obesity

In the SCALE Kids trial among children aged 6–11 years with obesity, 56-week treatment with liraglutide, in addition to lifestyle interventions, resulted in greater reductions in BMI and body weight than placebo.

This summary is based on the publication of Fox CK, Barrientos-Pérez M, Bomberg EM, et al. - Liraglutide for Children 6 to <12 Years of Age with Obesity — A Randomized Trial. N Engl J Med. 2024 Sep 10 [Online ahead of print]. doi: 10.1056/NEJMoa2407379

Introduction and methods

Background

As lifestyle interventions have only a modest long-term effect on obesity in children and adolescents [1-4], there is a need for additional treatment options. In recent years, the FDA and EMA have approved several GLP1-RAs, such as liraglutide, for long-term weight management in adults and adolescents with obesity [5-8]. However, there are currently no approved medications for the treatment of nonmonogenic, nonsyndromic obesity in children <12 years old.

Aim of the study

The study aims was to assess the efficacy and safety of liraglutide, as adjunct to lifestyle interventions, in younger children with obesity.

Methods

The SCALE Kids trial was an international, multicenter, double-blind, placebo-controlled, phase 3a RCT in which 82 children (aged 6–11 years) with obesity (defined as age- and sex-adjusted BMI in ≥95th percentile) were enrolled. Participants were randomized in a 2:1 ratio to treatment with subcutaneous liraglutide 3 mg (or maximum tolerated dose) once daily or placebo, in addition to lifestyle interventions, for 56 weeks, followed by a 26-week follow-up period. Exclusion criteria included T1D and secondary causes of obesity. For the principal analysis, the treatment policy estimand was used, which assessed the treatment effect regardless of discontinuation of the study drug or initiation of rescue interventions.

Outcomes

The primary efficacy endpoint was the percentage change in BMI. Confirmatory secondary efficacy endpoints were the percentage change in body weight and a BMI reduction ≥5%. Safety assessments included the frequencies of adverse events, serious adverse events, and adverse events leading to discontinuation of the study drug.

Main results

Efficacy

• At 56 weeks, the mean percentage change in BMI from baseline was –5.8% in children treated with liraglutide (n=56) and 1.6% in those receiving placebo (n=26) (estimated difference: –7.4 percentage points; 95%CI: –11.6 to –3.2; P<0.001).

• The mean percentage change in body weight from baseline to 56 weeks was 1.6% in the liraglutide group and 10.0% in the placebo group (estimated difference: –8.4 percentage points; 95%CI: –13.4 to –3.3; P=0.001).

• A BMI reduction ≥5% was found in 46% of the participants in the liraglutide group and 9% of those in the placebo group (adjusted OR: 6.3; 95%CI: 1.4–28.8; P=0.02).

Safety

• The frequency of adverse events during the treatment period was similar in the liraglutide and placebo group (89% vs. 88%), most of which were mild to moderate in severity and resolved with no apparent sequelae.

• The most common adverse events were gastrointestinal disorders, which were more frequently observed in the liraglutide group compared with the placebo group (80% vs. 54%).

• The rate of serious adverse events was 12% in the liraglutide group and 8% in the placebo group.

• In the liraglutide group, treatment was discontinued in 6 patients (11%), mostly because of gastrointestinal disorders. There were no adverse events leading to discontinuation in the placebo group.

Conclusion

In the SCALE Kids trial among children aged 6–11 years with obesity, 56-week treatment with liraglutide, in addition to lifestyle interventions, resulted in greater reductions in BMI and body weight than placebo. Furthermore, more patients in the liraglutide group achieved a BMI reduction ≥5% than those in the placebo group. There were no apparent safety concerns. The authors note that an open-label extension phase of this trial is ongoing, which is expected to be completed in January 2027.

Find this article online at N Engl J Med.

References

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5. Food and Drug Administration. Saxenda: highlights of prescribing information. December 2014 (https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/206321Orig1s000lbl.pdf).
6. European Medicines Agency. Saxenda: summary of product characteristics. December 2019 (https://www.ema.europa.eu/en/documents/product-information/saxenda-epar-product-information_en.pdf).
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8. European Medicines Agency. Saxenda. March 25, 2021 (https://www.ema.europa.eu/en/documents/smop/chmp-post-authorisation-summary-positive-opinion-saxenda-ii-26_en.pdf).