Endocrine Abstracts

JOINT506

Background: Insulin-like growth factor 1 (IGF-1) is a key marker of growth hormone (GH) activity, with its levels reflecting the efficacy and safety of GH therapies. Daily recombinant human GH (rGH) therapy provides steady IGF-1 levels, whereas long-acting weekly GH formulations (e.g., somapacitan, TransCon GH) show dose-dependent, cyclical IGF-1 responses. Understanding these patterns is crucial for optimizing treatment efficacy and safety.

Objective: To compare IGF-1 trends and cycles associated with daily and weekly GH therapies in terms of their patterns, peaks, and overall exposure (AUC).

Methods: Data were synthesized from eight studies analyzing IGF-1 response to various GH therapies, including daily rGH and weekly long-acting formulations such as somapacitan, PEG-rhGH, TransCon GH, and Nutropin Depot. Key metrics included IGF-1 levels before and after treatment, trends in weekly cycles, and AUC comparisons.

Results: • Weekly GH Therapies: Studies on somapacitan, TransCon GH, and PEG-rhGH demonstrated dose-dependent increases in IGF-1 levels, with a distinct cyclic pattern characterized by peaks around day 3-4 post-injection and gradual declines by day 7. These therapies maintained IGF-1 levels within the normal range and were associated with sustained efficacy and safety over long-term use-(Sävendahl et al., 2020; Chatelain et al., 2017).

• Daily GH Therapies: Daily rGH therapy (e.g., Genotropin, Norditropin) resulted in more consistent IGF-1 levels with minor daily fluctuations, providing a steady profile throughout the week-(Lundberg et al., 2018).

• Comparison of AUC: Weekly GH therapies exhibited a higher IGF-1 AUC due to pronounced peaks, while daily GH therapy maintained lower but more consistent IGF-1 levels. The higher AUC in weekly therapies indicates greater overall IGF-1 exposure, potentially enhancing efficacy but requiring careful monitoring to prevent side effects.

Discussion: Weekly GH therapies offer convenience and adherence benefits through reduced injection frequency while maintaining effective IGF-1 levels. However, the cyclic IGF-1 patterns and higher AUC necessitate careful patient monitoring to minimize risks associated with IGF-1 peaks. Daily rGH provides a stable IGF-1 profile, facilitating better fine-tuning, but at the cost of daily injections.

Conclusion: Both weekly and daily GH therapies effectively elevate IGF-1 levels, with distinct advantages and limitations. Weekly formulations optimize patient adherence and long-term exposure, whereas daily rGH ensures consistent IGF-1 profiles.