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
How does SCALE Teens compare with STEP-TEENS for semaglutide?
Both trials enrolled adolescents 12 to under 18 with obesity and tested a GLP-1 receptor agonist on top of lifestyle therapy, but the magnitudes differ substantially. SCALE Teens (Kelly 2020, PMID 32233338) randomized 251 adolescents to once-daily liraglutide 3.0 mg or placebo for 56 weeks and produced an estimated treatment difference in BMI of about 4.64 percentage points and a body-weight difference of about 5.01 percentage points. STEP-TEENS (Weghuber 2022, NEJM, PMID 36322838) randomized 201 adolescents to once-weekly semaglutide 2.4 mg or placebo for 68 weeks and produced an estimated treatment difference in body weight of about 17.4 percentage points, with 73% of semaglutide-treated adolescents reaching at least 5% weight loss versus 18% of placebo. Semaglutide produced roughly three-to-four times more relative weight loss than liraglutide in this age group, mirroring the adult STEP-1 vs SCALE-Obesity gap. The two trials together established that GLP-1 efficacy scales similarly between adolescents and adults, with semaglutide outperforming liraglutide in both age ranges.
Is Saxenda still preferred over Wegovy in pediatric obesity care?
Generally no, although Saxenda retains a role. Wegovy (semaglutide 2.4 mg) received its FDA pediatric indication for adolescents 12 and older in December 2022 based on STEP-TEENS, producing larger weight reductions and a weekly dosing schedule that simplifies adherence in adolescent populations where daily injection adherence is a known barrier. Saxenda (liraglutide 3.0 mg) is now most commonly used in pediatric practice when weekly semaglutide is not covered by insurance, when a slower titration is clinically preferred, or in younger adolescents whose families prefer the longer real-world track record of liraglutide, which carries pediatric data going back to the SCALE Teens 2020 publication and the Saxenda label expansion that followed in December 2020. American Academy of Pediatrics 2023 obesity guidance does not rank the two products head to head; both are listed as options.
Did the weight come back after stopping in SCALE Teens?
Partially, yes. The 26-week off-drug follow-up (weeks 56 to 82) showed an estimated treatment difference in BMI SDS rebound of +0.15 (95% CI 0.07 to 0.23), meaning adolescents who had stopped liraglutide regained more on the BMI z-score scale than adolescents who had stopped placebo. The rebound did not fully erase the on-treatment difference, but the direction was unambiguous and consistent with the adult evidence from STEP-1 off-treatment extension (Wilding 2022) and the SURMOUNT-4 withdrawal trial (Aronne 2024). The clinical implication is that pediatric anti-obesity pharmacotherapy is most likely a chronic intervention, similar to how stimulants are dosed for ADHD or insulin for type 1 diabetes — not a short course followed by discontinuation.
Why was BMI standard-deviation score the primary endpoint instead of percent weight loss?
Because adolescents are still growing in height during a 56-week trial, raw BMI can fall or stay stable simply because height increased while weight held steady. That makes BMI an inadequate single metric for the pediatric population. BMI SDS — also called BMI z-score — converts each participant's BMI into a standard-deviation distance from the WHO age- and sex-specific median, so a 13-year-old boy and a 17-year-old girl can be evaluated on the same scale and the effect of normal growth is taken out of the comparison. Pediatric endocrinology and obesity-medicine guidance from the WHO, the American Academy of Pediatrics, and the Endocrine Society all favor BMI SDS or BMI percentile as the primary measure in children and adolescents. Adult obesity trials use percent change in body weight because adult height is stable; pediatric trials use BMI SDS because it isn't.
What is the youngest age FDA-approved for any GLP-1 receptor agonist?
Twelve years for any GLP-1 for the obesity indication: Saxenda (liraglutide 3.0 mg) was approved for adolescents 12 and older in December 2020 on the basis of SCALE Teens, and Wegovy (semaglutide 2.4 mg) was approved for the same age range in December 2022 on the basis of STEP-TEENS. For type 2 diabetes the youngest age varies by product: Victoza (liraglutide 1.8 mg) was approved for pediatric type 2 diabetes ages 10 and older in June 2019, and Ozempic and Mounjaro currently remain adult-only for diabetes. Outside the GLP-1 class, the Endocrine Society and American Academy of Pediatrics 2023 obesity guidelines generally recommend considering anti-obesity pharmacotherapy starting at age 12. No GLP-1 receptor agonist is FDA-approved for children under 12 for either indication as of May 2026.
How did SCALE Teens influence the FDA Saxenda label and pediatric prescribing?
Directly. On December 4, 2020, eight months after the SCALE Teens NEJM publication, the FDA approved Saxenda for chronic weight management in adolescents 12 and older with body weight above 60 kg and a baseline BMI corresponding to the adult cutoff of 30 kg/m² by international growth charts. The label cites SCALE Teens (NN8022-4180) as the supporting pivotal trial and recommends weekly dose escalation across four weeks to the 3.0-mg maintenance dose, identical to the adult titration schedule. The pediatric indication also requires demonstrated response (at least 1% BMI SDS reduction after 12 weeks at the 3.0-mg maintenance dose) for continued treatment, a stopping rule unique to the pediatric label and intended to limit exposure in non-responders.
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.