Endocrine Abstracts

JOINT794

Background: Long-acting growth hormone (GH) therapy offers improved adherence and convenience compared to daily GH therapy, but it is associated with periodic IGF-1 fluctuations due to its extended release profile. The clinical safety of these fluctuations and their potential impact on adverse events remain important considerations in choosing therapy for GH deficiency (GHD).

Objective: To evaluate the safety profile of long-acting GH therapy compared to daily GH therapy, focusing on the implications of IGF-1 fluctuations and potential adverse outcomes.

Material and Methods: A comprehensive review of studies was conducted comparing safety profiles between long-acting GH therapies (e.g., somapacitan, TransCon GH) and daily GH therapies (e.g., Genotropin). Data were extracted on IGF-1 fluctuations, IGF-1 SDS excursions, and adverse events. The results are summarized in a comparison table.

Results: Key Findings:

1. Long-Acting GH Therapy:

• Fluctuations: Large IGF-1 peaks were observed post-injection, typically on days 3–4, with troughs approaching baseline by day 7.

• Safety: Minimal adverse events were reported despite IGF-1 SDS excursions >2.0 in some patients, particularly at higher doses.

• Specific Studies:

• Kildemoes et al. (2023): Weekly somapacitan showed transient IGF-1 SDS excursions >2.0 but was well-tolerated.

• Chatelain et al. (2017): IGF-1 SDS >2.0 occurred in 4/14 patients at the highest dose of TransCon GH, with no clinical adverse events or dose modifications.

• Adverse Events: Rare occurrences of injection-site reactions and mild transient hyperglycemia.

2. Daily GH Therapy:

• Fluctuations: Daily administration resulted in smaller, more consistent IGF-1 fluctuations, typically maintaining IGF-1 SDS <1.0.

• Safety: Well-tolerated with no IGF-1 SDS excursions above therapeutic thresholds.

• Specific Studies: Garner et al. (2023): No significant adverse events were observed, with stable IGF-1 levels within the therapeutic range.

Discussion: The larger IGF-1 fluctuations observed with long-acting GH therapies are generally transient and dose-dependent, with no significant safety concerns reported in short-term studies. Daily GH therapy exhibits a more stable IGF-1 profile, minimizing the risk of IGF-1 excursions but requiring frequent dosing. Long-term monitoring is necessary to assess the clinical implications of sustained IGF-1 peaks with long-acting therapies.

Conclusion: Long-acting GH therapy is a safe and effective alternative to daily GH therapy, despite larger IGF-1 fluctuations. Careful dose titration and regular monitoring are essential to minimize transient IGF-1 SDS excursions and maintain a favorable safety profile.