Objective To evaluate the clinical efficacy and safety of long-acting versus short-acting recombinant human growth hormone (rhGH) in treating children with idiopathic short stature (ISS).

Methods A total of 134 ISS patients were selected from the electronic medical record system of Guangdong Provincial People's Hospital affiliated to Southern Medical University from January 1, 2020 to December 31, 2024. Among them, 120 cases received rhGH therapy and were divided into two groups based on treatment regimen: the long-acting group (n = 75, treated with long-acting rhGH) and the short-acting group (n = 45, treated with short-acting rhGH). Efficacy and safety outcomes were compared between two groups at 6, 12, 18, and 24 months of follow-up.

Results In the long-acting group, significantly greater height improvements were observed at all follow-up time points compared to those in the short-acting group ［6 months: (119.32 ± 6.99) cm vs. (114.91 ± 3.49) cm; 12 months: (125.34 ± 7.11) cm vs. (119.73 ± 5.38) cm; 18 months: (128.00 ± 7.26) cm vs. (125.69 ± 4.42) cm; 24 months: (136.13 ± 7.45) cm vs. (131.98 ± 5.45 cm); all P ＜ 0.05］. Similarly, growth velocity (GV) in the long-acting group was significantly higher at each follow-up time point ［6 months: (11.29 ± 1.12) cm/year vs. (2.14 ± 2.56) cm/year; 12 months: (11.66 ± 1.82) cm/year vs. (5.89 ± 2.12) cm/year; 18 months: (9.54 ± 1.31) cm/year vs. (7.90 ± 1.23) cm/year; 24 months: (11.22 ± 1.21) cm/year vs. (9.07 ± 1.13) cm/year; all P ＜ 0.05］. For thyroid function, free triiodothyronine level at 6-month follow-up in the long-acting group was significantly higher than that in the short-acting group (P ＜ 0.05), with no significant differences at 12, 18, or 24 months. At 24-month follow-up, free thyroxine and thyroid stimulating hormone levels in the long-acting group were significantly lower than those in the short-acting group (both P ＜ 0.05). At 6- and 18-month follow-up, IGF-1 levels in the long-acting group were significantly higher compared with those in the short-acting group (both P ＜ 0.05). Except for the index differences at these time points, no statistical significance was observed in all indexes at other time points (all P ＞ 0.05).

Conclusion Long-acting rhGH demonstrates superior short-term (2 years) efficacy in promoting growth and development in children with ISS, with a favorable safety profile.