- Design
- Systematic review and random-effects network meta-analysis of RCTs
- Population
- 42 trials, 3,835 adolescents aged 10-19 with obesity
- Primary outcome
- BMI and BMI z-score
- Effect
- Semaglutide + counselling BMI −8.31 (−12.33 to −4.28); lifestyle alone −3.85 (−4.91 to −2.80)
A systematic review and network meta-analysis in JAMA Pediatrics (September 2026) pooled 42 randomised trials of 3,835 adolescents aged 10 to 19 with obesity, comparing lifestyle treatment, medications (GLP-1 receptor agonists, metformin, orlistat, phentermine-topiramate) and combinations against control.
Combined medication and lifestyle treatment gave the greatest effects on every adiposity outcome. Semaglutide with counselling produced the largest BMI reduction (mean difference −8.31 kg/m², 95% CI −12.33 to −4.28) and BMI z-score reduction (−1.80), though based on few studies. Every medication worked better with lifestyle treatment than alone. Lifestyle treatment by itself reduced BMI by 3.85 kg/m² (−4.91 to −2.80) against control.
Follow-up was typically 6 to 12 months, so durability after stopping medication and long-term safety in growing adolescents are not addressed. The semaglutide estimate rests on a small evidence base.
For a paediatrician, the message is two-sided: structured lifestyle treatment remains the foundation and is effective alone, and medication is most effective as an addition to it, not a replacement.
- Start every adolescent with obesity on a structured lifestyle programme involving the family
- Consider medication alongside — not instead of — lifestyle treatment for severe or complicated obesity
- Expect weight regain after stopping medication, and plan for it before starting
- Monitor growth, puberty, mood and eating behaviour in adolescents on GLP-1 agonists
- Offer lifestyle treatment even when medication is unaffordable — it reduced BMI by about 3.9 on its own
Why it matters
It shows pharmacotherapy is most effective when lifestyle treatment continues, answering whether medication makes lifestyle work redundant.
Don't overread it
Most trials ran 6 to 12 months, and the semaglutide estimate rests on few studies.
The statistics, in plain English
A BMI z-score measures how far a child's BMI sits from the average for age and sex; a fall of 0.89 with lifestyle alone is clinically meaningful. The semaglutide interval (−12.3 to −4.3 kg/m²) is wide because few trials contributed.
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