Long-Acting Growth Hormone Versus Daily Growth Hormone for Growth Hormone Deficiency Patients: A Network Meta-Analysis of Clinical Trials.
Weekly long-acting growth hormone may improve height velocity compared to daily somatropin, but clinicians should consider the risk of localized reactions and individual patient needs when selecting treatment.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This study evaluated the comparative efficacy and safety of long-acting growth hormone (LAGH) versus daily somatropin in children with growth hormone deficiency (CHD). The analysis included 18 randomized controlled trials (RCTs) with a total of 3137 participants. Key findings indicated that weekly YPEG-rhGH 0.1 mg/kg/week had a significantly higher height velocity compared to daily somatropin.
Abstract
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.
Background
This paper addresses the efficacy and safety of long-acting growth hormone formulations compared to daily somatropin in pediatric patients with growth hormone deficiency. Previous studies have established daily recombinant human growth hormone as the standard treatment, but the emergence of long-acting alternatives necessitates a thorough evaluation of their comparative effectiveness. Understanding these differences is crucial for clinicians in optimizing treatment strategies for growth hormone deficiency.
Methods
The study utilized a network meta-analysis design, synthesizing data from major databases including PubMed and Cochrane Central, with a search extending to April 2026. A total of 18 randomized controlled trials were included, comprising 3137 participants with CHD. The primary outcomes measured were height velocity, height SDS, and adverse events, with a focus on comparing various dosing regimens of LAGH against daily somatropin.
Results
The primary endpoint for height velocity showed that weekly YPEG-rhGH 0.1 mg/kg/week resulted in a significant increase with an SMD of 5.02 compared to daily somatropin. For IGF-1 SDS, Lonapegsomatropin 0.24 mg/kg/week significantly increased levels with an SMD of 0.74 [0.36-1.12]. No significant differences were found for height SDS among the treatments, and the safety profile indicated that Somatrogon was associated with a significantly increased risk of localized injection site erythema (RR: 10.55).
Interpretation
The findings suggest that while weekly YPEG-rhGH shows a statistically significant improvement in height velocity, the clinical significance of this effect should be carefully considered, especially given the potential for localized reactions with certain formulations. The lack of significant differences in height SDS and overall treatment discontinuation rates indicates that while LAGH may be a viable alternative, the choice of treatment should be individualized based on patient profiles and potential adverse effects. Confounding factors such as trial heterogeneity and the potential for bias in reporting outcomes may limit the generalizability of these results.
Key findings
- SMD: 5.02 for height velocity comparing weekly YPEG-rhGH 0.1 mg/kg/week to daily somatropin.
- SMD: 0.74 [0.36-1.12] for IGF-1 SDS with Lonapegsomatropin 0.24 mg/kg/week.
- RR: 10.55 for increased risk of localized injection site erythema with Somatrogon.
- No significant differences for height SDS across treatments.
- Overall discontinuation rates did not differ significantly between LAGH formulations and daily therapy.
Limitations
- Heterogeneity of included trials.
- Potential biases in reporting outcomes.
- Not all formulations were directly compared in every trial.
- Short follow-up duration may not capture long-term effects.