Liraglutide reduced BMI in adolescents with obesity in 56-week trial

Liraglutide 3.0 mg given daily reduced body mass index in adolescents with obesity more than placebo over 56 weeks, according to the SCALE TEENS trial published in the New England Journal of Medicine ^[1]. It was a phase 3 randomized, double-blind, placebo-controlled study, and the report describes it as testing liraglutide as an adjunct to lifestyle therapy in this age group ^[1].

The trial enrolled 251 adolescents aged 12 to under 18 at 32 sites in Belgium, Mexico, Russia, Sweden and the United States, running from September 29, 2016, through August 8, 2019 ^[1]. All participants had obesity, defined as a BMI at or above the 95th percentile for age and sex, stable body weight, and a poor response to lifestyle therapy alone as judged by the site investigator. They were randomly assigned 1:1 to liraglutide 3.0 mg or volume-matched placebo, both given as a once-daily injection, alongside counseling on healthy nutrition and physical activity. The study had a 12-week run-in, 56 weeks of treatment, then 26 weeks without treatment ^[1]. Adolescents with type 2 diabetes could enroll; type 1 diabetes was an exclusion ^[1].

The primary endpoint was the change from baseline in BMI standard-deviation score at week 56 — a measure of how far a child's BMI sits from the population average for their age and sex. Liraglutide was superior to placebo, with an estimated difference of −0.22 (95% CI, −0.37 to −0.08; P=0.002) ^[1][2].

On secondary measures, a BMI reduction of at least 5% occurred in 51 of 113 liraglutide participants and 20 of 105 placebo participants (estimated 43.3% vs. 18.7%); a reduction of at least 10% occurred in 33 and 9, respectively (estimated 26.1% vs. 8.1%). The estimated difference between groups was −4.64 percentage points for BMI and −4.50 kg for body weight, or −5.01 percentage points for relative weight change ^[1][2].

After treatment stopped, BMI standard-deviation score increased more in the liraglutide group than in the placebo group during the 26-week follow-up, with an estimated difference of 0.15 (95% CI, 0.07 to 0.23) ^[1][2].

Gastrointestinal adverse events were reported in 81 of 125 liraglutide participants (64.8%) versus 46 of 126 on placebo (36.5%). Adverse events that led to stopping treatment occurred in 13 liraglutide participants (10.4%) and none on placebo. Serious adverse events were uncommon in both groups: 3 (2.4%) with liraglutide and 5 (4.0%) with placebo. One suicide occurred in the liraglutide group; the investigator assessed it as unlikely to be related to trial treatment ^[1][2].

The statistical analysis plan did not include correction for multiple comparisons, and the report states that the confidence intervals for secondary endpoints should not be used to infer definitive treatment effects ^[1]. The trial was funded by Novo Nordisk and registered as NCT02918279 ^[1][2].

Why it matters for patients

Treatment options for adolescents with obesity are narrow. According to the trial report, orlistat and phentermine are the only FDA-approved medications for pediatric obesity, usable at age 12 and older and above age 16, respectively, and the European Medicines Agency has approved none; bariatric surgery is offered only for severe obesity and is performed infrequently ^[1]. That leaves few choices for teenagers who do not respond to lifestyle therapy alone, which is the group studied here ^[1].

The results also show a limit: weight loss was not maintained after the injections stopped, with BMI standard-deviation score rising again over 26 weeks off treatment ^[1][2]. The trial tested liraglutide only and does not provide data on semaglutide or tirzepatide in adolescents. Liraglutide 3.0 mg is given as a daily injection, unlike the once-weekly injections used for some other GLP-1 medications, and roughly one in ten adolescent participants on liraglutide stopped treatment because of adverse events ^[1].

What happens next

The longest follow-up described is the 26 weeks after treatment ended, so effects on growth, puberty and longer-term health in this age group have not been reported ^[1]. The trial report does not describe any regulatory filing or approval for adolescent use of liraglutide, and no data on cardiovascular outcomes in adolescents are included ^[1].