Pharmacological interventions for the management of children and adolescents living with obesity—An update of a Cochrane systematic review with meta-analyses

Importance: The effectiveness of anti-obesity medications for children and adolescents is unclear. Objective: To update the evidence on the benefits and harms of anti-obesity medication. Data Sources: Cochrane CENTRAL, MEDLINE, ClinicalTrials.gov and WHO ICTRP (1/1/16–17/3/23). Study Selection: Randomized controlled trials ≥6 months in people <19 years living with obesity. Data Extraction and Synthesis: Screening, data extraction and quality assessment conducted in duplicate, independently. Main Outcomes and Measures: Body mass index (BMI): 95th percentile BMI, adverse events and quality of life. Results: Thirty-five trials (N = 4331), follow-up: 6–24 months; age: 8.8–16.3 years; BMI: 26.2–41.7 kg/m². Moderate certainty evidence demonstrated a −1.71 (95% confidence interval [CI]: −2.27 to −1.14)-unit BMI reduction, ranging from −0.8 to −5.9 units between individual drugs with semaglutide producing the largest reduction of −5.88 kg/m² (95% CI: −6.99 to −4.77, N = 201). Drug type explained ~44% of heterogeneity. Low certainty evidence demonstrated reduction in 95th percentile BMI: −11.88 percentage points (95% CI: −18.43 to −5.30, N = 668). Serious adverse events and study discontinuation due to adverse events did not differ between medications and comparators, but medication dose adjustments were higher compared to comparator (10.6% vs 1.7%; RR = 3.74 [95% CI: 1.51 to 9.26], I² = 15%), regardless of approval status. There was a trend towards improved quality of life. Evidence gaps exist for children, psychosocial outcomes, comorbidities and weight loss maintenance. Conclusions and Relevance: Anti-obesity medications in addition to behaviour change improve BMI but may require dose adjustment, with 1 in 100 adolescents experiencing a serious adverse event.