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Research Article: Comparison of efficacy and safety between long-acting growth hormone and short-acting growth hormone in isolated growth hormone deficiency: a systematic review and meta-analysis of 16 randomized controlled trials involving 2,435 pediatric patients

Date Published: 2026-06-04

Abstract:
To comprehensively compare the efficacy and safety of long-acting human growth hormone (LAGH) preparations with conventional short-acting daily growth hormone (SA-GH) in children with isolated growth hormone deficiency (GHD), and explore potential differences across four distinct LAGH platforms through subgroup analyses. A systematic review and meta-analysis of randomized controlled trials (RCTs) published up to September 2025 was conducted. Five electronic databases [PubMed, Cochrane Library, Web of Science, WanFang Data, and China National Knowledge Infrastructure (CNKI)] were systematically searched without language restrictions. Eligible studies included patients aged <18 years with confirmed GHD (peak GH <10?ng·mL ?1 ) and compared any approved once-weekly LAGH preparation with daily SA-GH. Primary outcomes were changes from baseline in height velocity standard deviation score (HV-SDS) and height standard deviation score (Ht-SDS); secondary outcomes included insulin-like growth factor-1 (IGF-1) SDS and adverse events (AEs). Subgroup analyses were performed based on LAGH platform (PEG-LAGH, somatrogon, somapacitan, lonapegsomatropin) and treatment duration. A total of 16 RCTs involving 2,435 children (median follow-up: 52 weeks) were included. Overall, compared with SA-GH, LAGH resulted in a modest but statistically significant improvement in first-year Ht-SDS (mean difference [MD]: 0.08; 95% credible interval [CrI]: 0.04–0.11). Numerically, LAGH showed superior HV-SDS compared with SA-GH (MD: 0.85; 95% CrI: ?0.39 to 2.09), an effect entirely driven by the PEG-LAGH subgroup (MD: 4.35; 95% CrI: 3.78–4.92). IGF-1 SDS was consistently higher in the LAGH group (MD: 0.51; 95% CrI: 0.21–0.80). AE rates did not differ significantly between groups (LAGH: 31%–46% vs. SA-GH: 35%–50%); the PEG-LAGH subgroup exhibited the lowest AE incidence (31.1%). Among children with isolated GHD, LAGH represents the preferred platform, offering both superior first-year height velocity and acceptable safety. In contrast, newer prodrug or albumin-binding LAGH formulations provide injection convenience but lack superior growth efficacy.

Introduction:
Growth hormone deficiency (GHD) is one of the most common endocrine causes of childhood short stature, resulting from insufficient growth hormone secretion by the anterior pituitary gland and leading to impaired linear growth ( 1 , 2 ). Without timely intervention, affected children may attain a lifelong adult height below ?2 standard deviation scores (SDS) and experience psychosocial dysfunction ( 3 , 4 ). Since the introduction of recombinant human growth hormone (rhGH) in 1985, standardized daily subcutaneous…

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