Long‐Acting Growth Hormone Versus Daily Growth Hormone for Growth Hormone Deficiency Patients: A Network Meta‐Analysis of Clinical Trials

INTRODUCTION: Current guidelines recognize daily recombinant human growth hormone (rhGH) as standard care and long-acting growth hormone (LAGH) as an alternative for paediatric growth hormone deficiency (CHD). In this network meta-analysis (NMA), we updated the evidence to evaluate comparative efficacy and safety of multiple dosing nodes of LAGH versus daily somatropin. METHODS: Major databases, including PubMed, Embase, Cochrane Central, Scopus, Web of Science, and http://ClinicalTrials.Gov, were searched through April 2026 for randomized controlled trials (RCTs)in children with CHD. Outcomes included height velocity (HV), height SDS, and adverse events. Direct and indirect evidence was synthesized using a frequentist random-effects NMA (OSF: https://doi.org/10.17605/osf.io/nugpe). RESULTS: Eighteen RCTs (n = 3137) were analysed. In the primary random-effects model for HV, weekly YPEG-rhGH 0.1 mg/kg/week showed a significantly higher velocity compared to daily Somatropin (SMD: 5.02), whereas Somatrogon 0.25/0.48/0.66 mg/kg/week and Somapacitan 0.04 mg/kg/week showed lower HV. No significant differences were observed across treatments for height SDS. For IGF-1 SDS, Lonapegsomatropin 0.24 mg/kg/week significantly increased levels (SMD: 0.74 [0.36-1.12]), while Somatrogon and Somapacitan 0.04 mg/kg/week demonstrated reductions. Safety profiles showed that Somatrogon significantly increased the risk of localized injection site erythema (RR: 10.55) and pain. However, overall discontinuation rates did not differ significantly between LAGH formulations and daily therapy across the network. CONCLUSIONS: Once-weekly LAGH provides an effective frontline alternative to daily acting growth hormone, without compromising overall linear growth or safety, while displaying no differences in overall treatment discontinuation. Selection should be based on the patients' clinical profiles, specifically considering higher localized reactions with Somatrogon. Clinicians should adhere to formulation-specific sampling windows (2-5 days post dose for Lonapegsomatropin; 96 h for Somatrogon) to accurately monitor steady-state IGF-1 levels.