GLP-1s for Teenagers: the 10 Trials Behind the Approvals (2026)

The trial behind the approval: 201 teenagers aged 12 to 17 carrying obesity, given weekly semaglutide 2.4 mg or a placebo across 68 weeks, with lifestyle support in both arms. BMI fell 16.1% on the drug while rising 0.6% on placebo, and 73% of the treated group shed 5% or more of their body weight against 18%. It remains the largest phase 3 weight-management trial in this age group, and it produced the December 2022 pediatric label for Wegovy.

PMID 36322838 ↗NCT04102189 ↗DOI 10.1056/NEJMoa2208601 ↗

The trial that opened adolescent weight management to this class: 251 teenagers for whom lifestyle therapy had not worked, given daily liraglutide 3.0 mg or a placebo across 56 weeks — then watched a further 26 weeks with the drug taken away. BMI standard-deviation score fell 0.22 more than placebo and weight 4.5 kg more. ⛔ The off-treatment phase is the part worth carrying away: weight came back in both groups. The same rebound adult trials document happens here, in patients who may face sixty more years of it.

PMID 32233338 ↗NCT02918279 ↗DOI 10.1056/NEJMoa1916038 ↗

The first pediatric label in the class, and the template for everything after it. Liraglutide 1.8 mg daily went up against placebo over 26 weeks, plus a 26-week extension, in 134 patients aged 10 to 16 whose diabetes metformin had failed to control. A1C fell 0.64 points on the drug and rose 0.42 on placebo — a gap of 1.06 points. It produced the June 2019 Victoza pediatric indication and established that a pediatric program in this class could succeed.

PMID 31034184 ↗NCT01541215 ↗DOI 10.1056/NEJMoa1903822 ↗

A secondary analysis of STEP TEENS that reframed the result in terms a parent or a prior-authorization reviewer can act on. Rather than reporting BMI points, it counted how many teenagers crossed diagnostic lines: by week 68, 45% on semaglutide had dropped below the obesity threshold, 19.5% below the overweight threshold and 11.7% into the normal-weight range, against 12%, 1% and 0% on placebo. ★ That framing — moving out of a category rather than shaving a number — is what pediatric prescribing guidance now leans on.

PMID 37196421 ↗NCT04102189 ↗DOI 10.1002/oby.23808 ↗

Weekly exenatide 2 mg against placebo across 24 weeks in 83 patients aged 10 to 17, their diabetes managed by diet, metformin or long-acting insulin. A1C fell 0.36 points and rose 0.49 on placebo, a gap of 0.85. Its contribution is less the effect size than the format: it demonstrated that a once-weekly injection is workable in this age group, and it added a second drug to a pediatric toolkit that had exactly one.

PMID 35679098 ↗NCT01554618 ↗DOI 10.2337/dc21-2275 ↗

The only randomized GLP-1 data that exists in children under 12: 24 children aged 7 to 11 carrying obesity, given placebo or liraglutide titrated up to 3.0 mg, for five weeks. It was a phase 1 study — safety, tolerability and drug levels, not weight. Gastrointestinal effects dominated, and exposure at weight-adjusted dosing looked like adults'. ⛔ Twenty-four children over five weeks. It is a dosing study that informs future trials, and it is not evidence about treating children this age.

PMID 30653847 ↗DOI 10.1111/ijpo.12495 ↗

The comparator, not a drug trial. 242 teenagers aged 13 to 19 tracked prospectively after undergoing gastric bypass or a sleeve procedure for severe obesity. At three years weight was down 27%, with type 2 diabetes remitting in 95%, hypertension in 74% and dyslipidemia in 66%. This was the standard of care for severe adolescent obesity before these drugs existed, and it is the benchmark a 16% BMI reduction gets weighed against.

PMID 26544725 ↗NCT00474318 ↗DOI 10.1056/NEJMoa1506699 ↗

The follow-on comparison that made the case for operating earlier: 161 adolescents from Teen-LABS matched against 396 adults five years after the same procedure. Weight loss was similar — 26% against 29% — but the metabolic recovery was not. Type 2 diabetes remitted in 86% of adolescents against 53% of adults, and hypertension in 68% against 41%. ★ It is the strongest argument that metabolic disease is more reversible the earlier it is treated, which cuts both ways in the drug conversation.

PMID 31116917 ↗NCT00474318 ↗DOI 10.1056/NEJMoa1813909 ↗

The pooled randomized evidence across liraglutide, semaglutide and exenatide in children and adolescents with obesity, giving roughly a 5 to 6 kg/m² BMI advantage over placebo, with gastrointestinal effects the dominant tolerability finding. It is the reference regulators, pediatric societies and state Medicaid programs reach for when comparing agents, which makes it more consequential for access than its methods alone would suggest.

PMID 40269110 ↗DOI 10.1038/s41366-025-01790-w ↗

The 2026 update, folding in extension data and the exenatide youth trial. Pooled BMI reduction came out about 5% better than placebo, with a clear within-class ordering — semaglutide strongest, liraglutide in the middle, exenatide weakest — and blood pressure, lipids and liver enzymes improving alongside weight. It is the current benchmark for guideline panels deciding what a pediatrician should reach for first.

PMID 40588554 ↗DOI 10.1038/s41390-025-04228-1 ↗