Until 2020, severe adolescent obesity had almost no FDA-approved pharmacotherapy outside of phentermine (limited to short-term use age 16 and up) and metformin (off-label for weight). The pediatric drug pipeline opened in three steps. December 2014 brought liraglutide 1.8 mg for pediatric type 2 diabetes once Tamborlane's ELLIPSE trial published in 2019. December 2020 brought Saxenda (liraglutide 3.0 mg) for adolescent weight management after Kelly's SCALE Teens trial published in NEJM that May. December 2022 brought Wegovy (semaglutide 2.4 mg) for ages 12 and up after Weghuber's STEP TEENS phase-3 trial published in NEJM. Tirzepatide pediatric trials are ongoing as of 2026 with no FDA pediatric label yet. The ten papers below trace this arc: three pivotal phase-3 trials (STEP TEENS, SCALE Teens, ELLIPSE), three supporting analyses (Kelly 2023 BMI-threshold subanalysis, Tamborlane exenatide youth T2D, Mastrandrea ages 7-11), two Teen-LABS bariatric comparators that defined the pre-GLP-1 standard of care for severe pediatric obesity, and two 2025-2026 meta-analyses that quantify the pooled effect size across pediatric trials.
Ranked papers
#1STEP TEENS
Weghuber D, Barrett T, Barrientos-Pérez M, et al. · N Engl J Med · 2022
Primary endpoint: Percent change in BMI from baseline to week 68
STEP TEENS randomized 201 adolescents aged 12 to under 18 with obesity (BMI at or above the 95th percentile for age and sex) to semaglutide 2.4 mg weekly or placebo for 68 weeks alongside lifestyle counseling. BMI fell 16.1 percent on semaglutide versus a 0.6 percent rise on placebo, and 73 percent of treated participants lost at least 5 percent of body weight versus 18 percent on placebo. The trial drove the December 2022 FDA pediatric approval of Wegovy for ages 12 and up and remains the largest phase-3 GLP-1 adolescent weight-management trial.
PMID 36322838 ↗NCT04102189 ↗DOI 10.1056/NEJMoa2208601 ↗
#2SCALE Teens
Kelly AS, Auerbach P, Barrientos-Perez M, et al. · N Engl J Med · 2020
Primary endpoint: Change in BMI standard-deviation score at 56 weeks
SCALE Teens randomized 251 adolescents aged 12 to under 18 with obesity who had not responded to lifestyle therapy to liraglutide 3.0 mg daily or placebo for 56 weeks, followed by a 26-week off-treatment observation. Liraglutide reduced BMI standard-deviation score by 0.22 more than placebo and produced 4.5 kg greater absolute body-weight reduction. Discontinuation after week 56 caused weight regain in both groups. The trial supported the December 2020 FDA pediatric approval of Saxenda — the first GLP-1 weight-management indication for adolescents.
PMID 32233338 ↗NCT02918279 ↗DOI 10.1056/NEJMoa1916038 ↗
#3ELLIPSE
Tamborlane WV, Barrientos-Pérez M, Fainberg U, et al. · N Engl J Med · 2019
Primary endpoint: Change in glycated hemoglobin at 26 weeks
ELLIPSE randomized 134 children and adolescents aged 10 to under 17 with type 2 diabetes inadequately controlled on metformin (with or without basal insulin) to liraglutide 1.8 mg daily or placebo for 26 weeks, followed by a 26-week extension. HbA1c fell 0.64 percent on liraglutide and rose 0.42 percent on placebo — a 1.06 percentage point treatment difference. The trial drove the June 2019 FDA pediatric type-2-diabetes approval for Victoza, making liraglutide the first GLP-1 with any pediatric label and creating the regulatory template for SCALE Teens.
PMID 31034184 ↗NCT01541215 ↗DOI 10.1056/NEJMoa1903822 ↗
#4STEP TEENS (post-hoc)
Kelly AS, Arslanian S, Hesse D, et al. · Obesity (Silver Spring) · 2023
Primary endpoint: Proportion reaching BMI below the 95th, 90th, and 85th percentile at week 68
This pre-specified secondary analysis of STEP TEENS examined how many adolescents on semaglutide 2.4 mg crossed clinically meaningful BMI percentile thresholds. By week 68, 45 percent on semaglutide fell below the 95th percentile (obesity cutoff), 19.5 percent fell below the 85th percentile (overweight cutoff), and 11.7 percent reached the normal-weight range — versus 12, 1, and 0 percent on placebo. The paper supplied the clinically intuitive framing — moving teens out of an obesity class rather than just shaving BMI points — that anchored pediatric prescribing guidelines.
PMID 37196421 ↗NCT04102189 ↗DOI 10.1002/oby.23808 ↗
#5BCB114
Tamborlane WV, Bishai R, Geller D, et al. · Diabetes Care · 2022
Primary endpoint: Change in glycated hemoglobin at 24 weeks
This phase-3 trial randomized 83 youth aged 10 to under 18 with type 2 diabetes on diet, metformin, or basal insulin to once-weekly exenatide 2 mg or placebo for 24 weeks. HbA1c fell 0.36 percent on exenatide and rose 0.49 percent on placebo — a 0.85 percentage point treatment difference. The trial supported the 2021 FDA pediatric type-2-diabetes approval for Bydureon BCise, broadening the pediatric GLP-1 toolkit beyond liraglutide and demonstrating the weekly-injection paradigm is tolerable in youth.
PMID 35679098 ↗NCT01554618 ↗DOI 10.2337/dc21-2275 ↗
#6
Mastrandrea LD, Witten L, Carlsson Petri KC, et al. · Pediatr Obes · 2019
Primary endpoint: Tolerability and pharmacokinetics of liraglutide over 5 weeks
This phase-1 placebo-controlled trial randomized 24 children aged 7 to under 12 with obesity to liraglutide (titrated to 3.0 mg) or placebo for 5 weeks. The primary objective was safety, tolerability, and pharmacokinetics in a younger population than SCALE Teens enrolled. Gastrointestinal adverse events were the dominant tolerability signal and pharmacokinetic exposure was comparable to adults at body-weight-adjusted dosing. The trial supplies the only randomized GLP-1 data in pre-adolescent children and informs ongoing dosing work for the under-12 age band.
PMID 30653847 ↗DOI 10.1111/ijpo.12495 ↗
#7Teen-LABS
Inge TH, Courcoulas AP, Jenkins TM, et al. · N Engl J Med · 2016
Primary endpoint: Three-year body weight change after Roux-en-Y gastric bypass or sleeve gastrectomy
Teen-LABS prospectively followed 242 adolescents aged 13 to under 20 who underwent Roux-en-Y gastric bypass or sleeve gastrectomy for severe obesity. At three years, mean body weight fell 27 percent overall (28 percent gastric bypass, 26 percent sleeve), and most participants experienced remission of type 2 diabetes (95 percent), hypertension (74 percent), and dyslipidemia (66 percent). Teen-LABS defines the pre-GLP-1 standard of care for severe adolescent obesity and supplies the comparator against which Wegovy and Saxenda are now weighed in clinical decision-making.
PMID 26544725 ↗NCT00474318 ↗DOI 10.1056/NEJMoa1506699 ↗
#8Teen-LABS / LABS-2
Inge TH, Courcoulas AP, Jenkins TM, et al. · N Engl J Med · 2019
Primary endpoint: Five-year percent body weight change after Roux-en-Y gastric bypass
This linked analysis compared 161 adolescents in Teen-LABS to 396 adults in LABS-2 five years after Roux-en-Y gastric bypass. Adolescents and adults lost similar amounts of weight (26 versus 29 percent), but adolescents had significantly higher remission rates for type 2 diabetes (86 versus 53 percent) and hypertension (68 versus 41 percent). The paper established the case for earlier surgical intervention in eligible adolescents and frames the GLP-1 alternative: comparable durable weight loss without surgical morbidity, at the cost of indefinite drug therapy.
PMID 31116917 ↗NCT00474318 ↗DOI 10.1056/NEJMoa1813909 ↗
#9
Sedenho-Prado LG, Bottino LG, Diehl LA, et al. · Int J Obes (Lond) · 2025
Primary endpoint: Pooled BMI and weight change in pediatric GLP-1 randomized trials
This 2025 systematic review pooled randomized trials of GLP-1 receptor agonists (liraglutide, semaglutide, exenatide) in children and adolescents with obesity. The meta-analysis quantified roughly a 5 to 6 kg/m squared advantage on BMI for active treatment versus placebo across pooled trials, with gastrointestinal adverse events the dominant tolerability signal. Provides the highest-tier pooled evidence the FDA and AAP cite when comparing relative efficacy across pediatric GLP-1 agents and remains a key reference for state Medicaid prior-authorization framing.
PMID 40269110 ↗DOI 10.1038/s41366-025-01790-w ↗
#10
Romariz LM, Carvalho LSF, Cintra RM, et al. · Pediatr Res · 2026
Primary endpoint: Pooled change in BMI, body weight, and cardiometabolic markers
This 2026 Pediatric Research meta-analysis updated the pooled pediatric GLP-1 evidence to include the latest STEP TEENS extension data, the Tamborlane exenatide youth T2D trial, and emerging registry data. Pooled BMI reduction was about 5 percent greater than placebo with semaglutide leading the within-class effect size, liraglutide intermediate, and exenatide weakest. Cardiometabolic markers (blood pressure, lipids, ALT) all improved alongside weight. The paper supplies the most current pooled effect-size benchmark for pediatric obesity guideline panels weighing first-line drug selection.
PMID 40588554 ↗DOI 10.1038/s41390-025-04228-1 ↗
About this list
We curate ranked, citation-anchored PubMed paper lists for the most-searched questions in obesity medicine. Every citation on this page was checked against PubMed on 2026-05-28. Each paper card links directly to PubMed and to ClinicalTrials.gov where applicable.
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