medwireNews: Use of the glucagon-like peptide (GLP)-1 receptor agonist liraglutide alongside diet and exercise guidance significantly reduces BMI in children aged 6 to 11 years with severe obesity compared with lifestyle interventions alone, shows the SCALE Kids Trial.
The phase 3a study focused on children with an age- and sex-adjusted BMI in the 95th or higher percentile with Tanner stage 1–5 puberty but no evidence of type 1 diabetes, or monogenic or syndromic causes of obesity.
Timothy Barrett (University of Birmingham, UK) and Julian Hamilton-Shield (University of Bristol, UK) write in an editorial accompanying the research published in The New England Journal of Medicine: “We know that among adolescents with obesity, the most rapid weight gain occurs from 2 to 6 years of age, and most children with obesity at a young age have obesity in adolescence.”
They believe the findings “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.”
The children were randomly assigned to receive subcutaneous liraglutide 3.0 mg/day (or the maximum tolerated dose during titration from 0.6 mg/day) or placebo for 56 weeks to accompany individual counselling encouraging 60 minutes of moderate-to-high intensity exercise per day and a healthy diet. A 26-week follow-up of the study population is ongoing and expected to complete in January 2027.
Half (54%) of the participants were boys, the average age was 10 years and 72% were White. The children had an average BMI of 31.0 kg/m2 and the participants were split between obesity class 1 (≥95% to <120% of the 95th percentile; 24%), class 2 (≥120% to <140%; 37%) and class 3 (≥140%; 39%). In addition, 26% had one obesity-related complication at screening, 17% had two and 12% had three or more; none of the children had type 2 diabetes but 20% had insulin resistance, 12% had impaired glucose tolerance and 12% had precocious puberty.
The estimated mean percentage change in BMI between baseline and week 56 of treatment was a 5.8% decrease for the 56 patients given liraglutide versus a 1.6% increase for the 26 controls, giving a significant estimated difference of –7.4 percentage points in favour of the GLP-1 receptor agonist.
This was accompanied by an estimated average percentage change in body weight of 1.6% with liraglutide versus 10.0% with placebo, giving a significant estimated difference of –8.4 percentage points, again supporting liraglutide use.
Almost half (46%) of the liraglutide-treated children reduced their BMI by at least 5% versus just 9% of the controls, so liraglutide use was associated with a significant 6.3-fold greater likelihood of reaching this endpoint. And liraglutide was associated with a 14.0 percentage point reduction in BMI percentage of 95th percentile versus a 4.0 percentage point reduction with placebo.
During the follow-up phase, both treatment arms experienced gains in BMI and bodyweight, say Claudia Fox (University of Minnesota Medical School, Minneapolis, USA) and co-authors. For example, between baseline and week 56, liraglutide and placebo were associated on average with observed –6.7% and +2.1% changes in BMI, respectively, changing to –0.8% and +6.7% at week 82.
The researchers point out that “BMI as a percentage of the 95th percentile continued to be lower in the liraglutide group than in the placebo group during the follow-up period, which points to a sustained treatment benefit with liraglutide.”
But they note that the BMI as a percentage of the 95th percentile was “still greater than 120% at the end of the treatment period in the liraglutide group, which highlights the continued need for prioritizing research for effective treatments.”
Fox and team also found possible cardiometabolic benefits with liraglutide use versus placebo at week 56, namely improvements from baseline in diastolic (–1.2 vs 3.0 mmHg) and systolic (–1.7 vs 1.7 mmHg) blood pressure and glycated haemoglobin (–0.2 vs –0.1 %).
Overall, 89% of both treatment groups reported adverse events (AEs), mainly mild or moderate side effects that resolved. Gastrointestinal AEs were more common with liraglutide than placebo (80 vs 54%), with nausea and vomiting reported mostly during dose escalation.
Three serious AEs – two cases of vomiting and one of colitis – were considered possibly or probably related to liraglutide and six patients discontinued liraglutide because of AEs, with three due to gastrointestinal AEs.
The children in the liraglutide and placebo trial arms had similar changes in height, height standard deviation score, bone age, pubertal status and menarche over the study. This suggests that “liraglutide had no apparent adverse effects on growth and development when evaluated after 56 weeks”, say Fox et al.
Nevertheless, the researchers emphasize that “[l]ong-term studies evaluating the efficacy and safety of liraglutide in children and any potential effects on growth patterns are needed, as is postmarketing surveillance.”
By Lynda Williams
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