Efficacy and Safety of Pharmacological Interventions in Managing Cardiometabolic Risk Factors in Youth Living with Overweight and Obesity: A Systematic Review and Network Meta‐Analysis

ABSTRACT Background Obesity has become a growing global health concern among young people. This meta‐analysis seeks to systematically assess the efficacy and safety of pharmaceutical interventions in improving body weight, body mass index (BMI), waist circumference (WC), diastolic blood pressure (DBP), fasting blood glucose (FBG), and lipid profiles, planned prior to data collection. Methods We conducted a comprehensive literature search on PubMed, Scopus, Embase, Web of Science, and the Cochrane Library, covering studies published up to September 2024. Randomized clinical trials (RCTs) were included if they reported efficacy of weight‐loss medications in youth populations aged 2–20 years. Direct and indirect evidence were synthesized using a frequentist framework. Results Pooled analysis on 30 RCTs showed that high dose phentermine/topiramate was more effective in reducing weight (MD: −15.8 kg; 95%CI: −19.17 to −12.43), BMI (MD = −5.35 kg/m2; 95% CI: −8.03, −2.67), WC (MD = −7.69 cm; 95% CI: −10.19, −5.18), and BMI percentile (MD: ‐20.25; 95%CI: −24.82 to 95% CI: −20.38 to −1.62) compared to placebo. Orlistat (MD = −1.81 mmHg; 95% CI: −2.94, −0.68), metformin (MD: −0.14 unit; 95%CI: −0.23 to −0.04), liraglutide (MD: −11.00 mg/dL; 95% CI: −20.38 to −1.62) were more effective in improving DBP, BMI‐z score, and FBG, respectively. Lipid profile and SBP were not affected by studied drugs. Conclusion High‐ and moderate‐dose phentermine/topiramate was more effective than a placebo in reducing anthropometric measures in youth living with overweight and obesity. Liraglutide and metformin result in a significant reduction in FBG levels compared to placebo.