SCALE Teens deep-dive: liraglutide 3.0 mg in adolescents (Kelly 2020 NEJM)
Last verified 2026-05-28 · Phase 3 · Completed; primary results reported March 31, 2020 (NEJM) · NCT02918279 ↗
SCALE Teens (NN8022-4180, NCT02918279) is the phase-3 randomized trial that extended liraglutide's chronic-weight-management indication into the pediatric population. Novo Nordisk enrolled 251 adolescents 12 to under 18 years of age with obesity and a poor response to lifestyle therapy alone, randomizing them 1:1 to once-daily subcutaneous liraglutide 3.0 mg or matching placebo for 56 weeks of treatment plus 26 weeks of off-drug follow-up, all layered on standardized lifestyle counseling. The primary endpoint was the change from baseline in the body-mass-index standard-deviation score (BMI SDS) at week 56. Results published by Kelly and colleagues in the New England Journal of Medicine on March 31, 2020 showed an estimated treatment difference of -0.22 in BMI SDS (95% CI -0.37 to -0.08; P=0.002), supporting the December 2020 FDA expansion of the Saxenda label to adolescents ages 12 and older.
- Enrollment
- 251
- Duration
- 56-week double-blind treatment period plus 26-week off-drug follow-up (week 82 final visit)
- Drug
- Liraglutide 3.0 mg (Saxenda)
- Population
- Adolescents 12 to under 18 years of age with obesity (defined as BMI corresponding to at least 30 kg/m² for adults by international cut-offs) and a poor response to lifestyle therapy alone. Tanner stage 2 or higher was required; participants with type 1 or type 2 diabetes, secondary obesity, prior anti-obesity medication exposure within 3 months, or active major psychiatric disease were excluded. Mean age was approximately 14.5 years, mean baseline BMI roughly 35.3 kg/m², mean body weight 99.3 kg, and 56-57% of the cohort was female. Recruitment spanned Belgium, Mexico, Russia, Sweden, and the United States.
Primary endpoint
Change from baseline in BMI standard-deviation score (BMI SDS) at week 56
Treatment arm
Estimated change -0.23
Comparator
Estimated change -0.00
Treatment difference: Estimated treatment difference -0.22 (95% CI -0.37 to -0.08); P=0.002
BMI SDS is the primary pediatric obesity endpoint because adolescents are still growing in height. Expressing BMI as a z-score against age- and sex-specific WHO reference distributions adjusts for normal developmental BMI gain and lets a 14-year-old's response be compared on the same scale as a 17-year-old's. The -0.22 difference cleared the prespecified superiority margin and supported the December 2020 FDA pediatric indication for Saxenda.
Secondary endpoints
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| Participants achieving at least 5% reduction in baseline BMI at week 56 Pediatric obesity-medicine guidelines treat a 5% BMI reduction as a clinically meaningful response threshold; SCALE Teens more than doubled the responder rate versus lifestyle therapy alone. | 43.3% (51 of 113 evaluable) | 18.7% (20 of 105 evaluable) | Estimated odds ratio favoring liraglutide; nominal P<0.001 |
| Participants achieving at least 10% reduction in baseline BMI at week 56 | 26.1% (33 of 113 evaluable) | 8.1% (9 of 105 evaluable) | Roughly 3-fold higher proportion on liraglutide |
| Change from baseline in BMI at week 56 (kg/m² as a percentage) | Estimated -4.29 percentage-point relative reduction | Estimated +0.35 percentage-point relative change | Estimated treatment difference -4.64 percentage points (BMI relative change) |
| Absolute body-weight change at week 56 (kg) Placebo participants gained weight on average across the 56 weeks, consistent with the natural BMI trajectory of adolescents with obesity continuing to add lean mass and weight with growth; liraglutide bent that curve downward. | Estimated mean change -2.26 kg | Estimated mean change +2.25 kg | Estimated treatment difference -4.50 kg favoring liraglutide |
| Relative body-weight change at week 56 (percent) | Estimated -2.65% | Estimated +2.37% | Estimated treatment difference -5.01 percentage points favoring liraglutide |
| Change in BMI SDS from week 56 to week 82 (off-drug follow-up rebound) 26 weeks after discontinuation, BMI SDS rose more in the former-liraglutide group than in the former-placebo group, a regain pattern later replicated across STEP-TEENS, STEP-1 extension, and SURMOUNT-4. Obesity behaves as a chronic disease; the SCALE Teens follow-up was an early pediatric demonstration of that principle. | Estimated +0.22 SDS | Estimated +0.07 SDS | Estimated treatment difference +0.15 (95% CI 0.07 to 0.23) — greater rebound in the liraglutide group after stopping |
| Cardiometabolic parameters at week 56 (blood pressure, lipids, HbA1c) The absence of cardiometabolic signal in SCALE Teens partly reflects healthier baseline values in adolescents and the smaller sample size compared with the 3,731-participant adult SCALE trial. | No statistically significant between-group differences reported for systolic blood pressure, lipid panel, or HbA1c | Reference | Cardiometabolic secondary endpoints did not show separation in this 56-week pediatric cohort, in contrast to the adult SCALE Obesity and Prediabetes trial (Pi-Sunyer 2015, PMID 26132939) where blood-pressure and lipid signals emerged |
| Health-related quality of life (PedsQL and IWQOL-Kids) at week 56 Both arms improved on patient-reported quality-of-life instruments, consistent with the well-documented placebo effect of structured lifestyle intervention in adolescent obesity trials. | Numerical improvements reported in liraglutide group | Numerical improvements also reported in placebo group | Between-group differences were not statistically significant on prespecified quality-of-life domains |
Adverse events
| Event | Treatment rate | Comparator rate |
|---|---|---|
| Any gastrointestinal adverse event Nausea, vomiting, and diarrhea were the most common GI events; the absolute and relative excess in the liraglutide group mirrors the adult SCALE program. | 64.8% (81 of 125) | 36.5% (46 of 126) |
| Nausea Most events were mild-to-moderate and concentrated in the 4-week dose-escalation phase, consistent with the adult Saxenda label. | Approximately 42% of liraglutide arm (per supplementary AE table) | Approximately 14% of placebo arm |
| Vomiting Largest relative GI excess versus placebo; resolved over time in most participants. | Approximately 34% of liraglutide arm | Approximately 4% of placebo arm |
| Diarrhea | Approximately 22% of liraglutide arm | Approximately 14% of placebo arm |
| Adverse event leading to trial-product discontinuation All discontinuations in the liraglutide arm were for treatment-emergent events, predominantly GI. | 10.4% (13 of 125) | 0% (0 of 126) |
| Serious adverse events (any) Serious-event rate was numerically lower on liraglutide than on placebo and below adult SCALE-program rates. | 2.4% (3 of 125) | 4.0% (5 of 126) |
| Death Investigators assessed the single suicide as unlikely to be related to trial treatment. Adolescent suicidality remains a labeled concern across anti-obesity medications and was monitored prospectively in SCALE Teens with the Columbia Suicide Severity Rating Scale. | 1 (suicide in liraglutide arm) | 0 |
| Hypoglycemia (any) Adolescents with type 1 or type 2 diabetes were excluded, so symptomatic hypoglycemia was uncommon in either arm. | Low and similar across arms | Low and similar across arms |
Subgroup analyses
- Age 12 to under 15 vs age 15 to under 18: Treatment effect on BMI SDS was consistent across the younger and older adolescent strata
Supports the FDA decision to label Saxenda for the full 12 and older pediatric range rather than restricting to the 15-and-older subgroup.
- Tanner stage at baseline (pubertal status): Treatment effect was consistent across Tanner stages 2 through 5 in the prespecified analyses
Important because pubertal hormonal changes alter body composition and could plausibly modify drug response; SCALE Teens did not detect modification.
- Sex (male vs female): Treatment effect on BMI SDS favored liraglutide in both sexes with overlapping confidence intervals
No statistically meaningful sex-by-treatment interaction reported.
- Baseline BMI category: Treatment effect was directionally similar across baseline BMI quartiles, with the largest absolute kilogram-weight differences in the highest-BMI subgroups
Reflects the general pattern in obesity trials that participants with higher baseline weight have more absolute weight to lose.
Clinical significance
SCALE Teens is the trial that opened the modern era of pediatric anti-obesity pharmacotherapy. Before SCALE Teens reported in 2020, the only FDA-approved chronic anti-obesity medication for adolescents was orlistat, with modest effect sizes and meaningful gastrointestinal tolerability problems. Liraglutide 3.0 mg cleared the prespecified superiority margin on BMI SDS, produced a clinically meaningful doubling of the proportion of adolescents reaching at least 5% BMI reduction, and supported the December 2020 FDA expansion of Saxenda to adolescents 12 and older. The off-drug rebound seen at week 82 was the first phase-3 demonstration in adolescents that GLP-1 obesity therapy behaves as a chronic-disease treatment. SCALE Teens directly seeded the design of STEP-TEENS (Weghuber 2022, PMID 36322838), which extended the paradigm to semaglutide 2.4 mg and produced a roughly threefold larger mean BMI reduction in the same age range. As of May 2026, the youngest FDA-approved age for any GLP-1 receptor agonist for obesity remains 12 years, with both Saxenda and Wegovy carrying pediatric labels.
Frequently Asked Questions
References
- 1.Kelly AS, Auerbach P, Barrientos-Perez M, Gies I, Hale PM, Marcus C, Mastrandrea LD, Prabhu N, Arslanian S; NN8022-4180 Trial Investigators A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity N Engl J Med 2020;382(22):2117-2128. 2020. PMID: 32233338.
- 2.ClinicalTrials.gov Effect of Liraglutide for Weight Management in Pubertal Adolescent Subjects With Obesity (NN8022-4180) ClinicalTrials.gov, NCT02918279. 2020. https://clinicaltrials.gov/study/NCT02918279
- 3.Weghuber D, Barrett T, Barrientos-Pérez M, et al. Once-Weekly Semaglutide in Adolescents with Obesity N Engl J Med 2022;387(24):2245-2257. 2022. PMID: 36322838.
- 4.U.S. Food and Drug Administration Saxenda (liraglutide) injection 3 mg — Prescribing Information (pediatric label expansion) DailyMed. 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=51eb02c8-3c74-4a01-bb55-13c9c9e3f74c
- 5.Hampl SE, Hassink SG, Skinner AC, et al. Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity Pediatrics 2023;151(2):e2022060640. 2023. PMID: 36622135.