Incretin receptor agonists in adolescents
In adolescents with obesity, what is the effect of an incretin receptor agonist on body-mass index, and what is known about growth, bone accrual and pubertal outcomes?
§1Abstract
§1.1Review question
In adolescents with obesity, what is the effect of an incretin receptor agonist on body-mass index, and what is known about growth, bone accrual and pubertal outcomes?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Adolescents aged 12 to under 18 years with obesity. |
| Intervention | Semaglutide 2.4 mg or liraglutide 3.0 mg. |
| Comparator | Placebo with a lifestyle intervention in both arms. |
| Outcomes | Percentage change in body-mass index; change in body-mass index standard-deviation score; height velocity; bone mineral density; pubertal staging; psychological outcomes. |
§1.3Method in brief
A review of the effects of an intervention on pre-specified outcomes, with a quantitative synthesis where the contributing studies are sufficiently similar. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 9 July 2025 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.[1]
§1.4Conclusion
Moderate certainty evidence indicates a substantial reduction in body-mass index over 56 to 68 weeks, larger in absolute terms than that observed in adults for the same agent. The Institute downgrades one level for indirectness with respect to the outcomes that matter most in this population: no contributing trial reported height velocity, bone accrual or pubertal progression beyond the randomised period, and the duration of exposure required is measured in years while the evidence is measured in months.
The conclusion rests on 2 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
§1.6Consultation
This review was released for public comment before ratification. Draft synthesis: incretin receptor agonists in adolescents received 16 submissions. Amendments arising are recorded in the amendment log and are traceable to a numbered submission.
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Weghuber D, Barrett T, Barrientos-Pérez M, Gies I, Hesse D, Jeppesen OK, Kelly AS, Mastrandrea LD, Sørrig R, Arslanian S. Once-weekly semaglutide in adolescents with obesity. New England Journal of Medicine 2022;387(24):2245–2257. doi:10.1056/NEJMoa2208601 · PMID 36322838
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.