Endocrinology · Medical Literature
Long-Acting Growth Hormone Versus Daily Growth Hormone for Growth Hormone Deficiency Patients: A Network Meta-Analysis of Clinical Trials.
Abstract
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. 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). 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. 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.
Clinical relevance
This network meta-analysis directly addresses the growing clinical need to compare multiple long-acting growth hormone (LAGH) formulations against standard daily recombinant human growth hormone (rhGH) in pediatric growth hormone deficiency (GHD), a population where treatment adherence to daily injections is a well-recognized barrier. By synthesizing data from 18 RCTs (n=3,137), it provides the most comprehensive comparative efficacy and safety evidence to date across distinct LAGH agents and doses. Clinicians prescribing growth hormone therapy in children now have actionable, formulation-specific data to guide individualized treatment selection.
Key findings
1. YPEG-rhGH 0.1 mg/kg/week demonstrated significantly higher height velocity (HV) compared to daily somatropin (SMD: 5.02), making it the highest-performing LAGH agent for linear growth velocity in this NMA. 2. Somatrogon (0.25, 0.48, and 0.66 mg/kg/week) and Somapacitan 0.04 mg/kg/week were associated with lower HV compared to daily somatropin, suggesting dose- and formulation-dependent efficacy differences. 3. No statistically significant differences were observed across any LAGH treatment versus daily somatropin for height SDS, indicating equivalent long-term height gain outcomes across formulations. 4. Lonapegsomatropin 0.24 mg/kg/week significantly increased IGF-1 SDS compared to daily somatropin (SMD: 0.74; 95% CI: 0.36–1.12), while Somatrogon and Somapacitan 0.04 mg/kg/week demonstrated reductions in IGF-1 SDS. 5. Somatrogon was associated with a significantly elevated risk of localized injection site erythema (RR: 10.55) and injection site pain compared to daily therapy, representing the most clinically notable safety signal across the network. 6. Overall treatment discontinuation rates did not differ significantly between any LAGH formulation and daily somatropin across the entire network, supporting the tolerability of once-weekly regimens.
Practice implications
Once-weekly LAGH formulations represent a clinically viable and guideline-consistent frontline alternative to daily somatropin in pediatric GHD, particularly for patients or families in whom adherence to daily injections is a concern, without compromising overall linear growth or treatment retention. Clinicians should exercise formulation-specific caution when selecting Somatrogon in patients with skin sensitivity or needle-aversion, given its substantially elevated risk of localized injection site erythema (RR: 10.55), and should counsel families accordingly. IGF-1 monitoring must adhere strictly to formulation-specific pharmacokinetic sampling windows — 2–5 days post-dose for Lonapegsomatropin and 96 hours post-dose for Somatrogon — to ensure accurate steady-state IGF-1 measurement and avoid erroneous dose titration decisions.