- Design
- Systematic review and random-effects network meta-analysis of randomised trials
- 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) vs control
A network meta-analysis pooled 42 randomised trials in 3,835 adolescents aged 10 to 19 with obesity, comparing structured lifestyle treatment, medications (GLP-1 receptor agonists, metformin, orlistat, phentermine–topiramate) and their combinations.
Combinations of medication and lifestyle treatment gave the greatest reductions across every adiposity outcome. Semaglutide with counselling was associated with the largest fall in BMI (−8.3 kg/m²) and BMI z score (−1.8), though from few studies. Every drug did better with lifestyle support than alone. Lifestyle treatment by itself still reduced BMI by 3.9 kg/m² against control.
The message for clinic is not 'drugs instead of lifestyle' but 'drugs on top of lifestyle' for adolescents who need more. Most trials ran 6 to 12 months, so durability after stopping remains unknown, and in India cost and access to GLP-1 agonists will limit use.
- Start every adolescent with obesity on structured family-based lifestyle treatment
- Consider medication when obesity is severe or comorbidities are present, alongside lifestyle support
- Screen for blood pressure, glucose, lipids, liver enzymes and sleep apnoea
- Plan for long-term treatment; weight tends to return when medication stops
- Watch for disordered eating and low mood
Why it matters
Medication without lifestyle support underperformed in every comparison, which reframes how it should be prescribed.
Don't overread it
The semaglutide estimate rests on few trials, and follow-up was mostly under a year.
The statistics, in plain English
A BMI z score shows how far a child's BMI is from the average for age and sex, in standard deviations. A fall of 0.9 with lifestyle alone is clinically meaningful; 1.8 with semaglutide plus counselling is large. The wide interval for semaglutide (−12.3 to −4.3 kg/m²) reflects few studies. Network meta-analysis combines direct and indirect comparisons, so rankings between drugs never directly compared are less certain.
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