Semaglutide 2.4mg SC leads weight loss in obese adolescents; Dulaglutide 1.5mg SC best for HbA1c.

Childhood and adolescent obesity is a growing global health crisis, significantly increasing the risk of type 2 diabetes (T2D), cardiovascular disease, and other cardiometabolic complications. Current lifestyle interventions often fall short, necessitating pharmacological options. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially for T2D, are now approved for weight management in this population, but their comparative efficacy and safety profiles across different agents for various cardiometabolic outcomes remain unclear, posing a challenge for clinical decision-making.

Researchers conducted a network meta-analysis of 17 randomized clinical trials involving 1230 participants (adolescents with overweight or obesity, with or without T2D). They systematically searched five major databases up to May 2026 for studies comparing GLP-1RAs against placebo or other active agents. Data extraction and risk of bias assessment followed PRISMA guidelines. A Bayesian random-effects model was used for data synthesis, comparing the effects of various GLP-1RAs on body weight, BMI, waist circumference, HbA1c, fasting plasma glucose, blood pressure, and lipid profiles.

The network meta-analysis revealed differential cardiometabolic benefits among GLP-1RAs in adolescents. Semaglutide 2.4mg SC demonstrated the most substantial impact on weight-related outcomes, leading to a mean reduction of -18.00kg (95% credible interval -24.34 to -11.69) in body weight, -5.9kg/m^2 (-10.5 to -1.3) in BMI, and -12.2cm (-21.67 to -2.67) in waist circumference, all with high confidence. For glycemic control, Dulaglutide 1.5mg SC showed the largest reduction in HbA1c at -1.50% (-1.84 to -1.15, high confidence).