In pediatric diabetes, long-acting insulin formulations such as insulin degludec have improved glycemic control stability as the longest-acting insulin analog while allowing for mixing with other formulations [1,2]. The introduction of 3-month and 6-month formulations of gonadotropin-releasing hormone agonist in the treatment of central precocious puberty has helped overcome the challenge of maintaining a strict dosing schedule every 4 weeks, greatly reducing the burden on patients and caregivers during long-term treatment [3].

For inherited metabolic disorders such as Fabry disease, enzyme replacement therapy, which has traditionally been administered every 2 weeks, is undergoing clinical trials to extend the half-life through pegylation, increasing the dosing interval to every 4 weeks. This adjustment is expected to positively impact treatment adherence by reducing the stress of frequent hospital visits and injections [4]. As such, the strategy of extending drug half-life is not merely a pharmacologic improvement; it is directly related to enhancing patient care and the overall treatment experience.

The field of growth hormone (GH) therapy has been exploring the transition from daily to long-acting formulations, with somatrogon as a notable example [5,6]. Maniatis et al. [7] reviewed the clinical significance and prospects of the latest long-acting formulations, focusing on clinical trials of somatrogon, which demonstrated noninferior efficacy compared to daily somatropin. Somatrogon, a long-acting GH analog, is an alternative treatment for pediatric GH deficiency (pGHD). It is engineered by fusing human GH with 3 copies of the carboxyl-terminal peptide from the β-subunit of human chorionic gonadotropin, resulting in a 47.5-kDa molecule [5,6]. Administered once weekly at a dose of 0.66 mg/kg/wk, it has demonstrated significant height gain comparable to daily GH therapy in global phase II, phase III, and Japanese phase III trials [8-10]. A preclinical comparison study showed similar height velocity (HV) between somatrogon (0.66 mg/kg/wk) and somatropin (0.24 mg/kg/wk), with values of 11.9±3.5 cm/yr and 12.5±2.1 cm/yr, respectively [8]. The global phase III trial also showed an HV of 10.1 cm/ yr after 12 months for somatrogon, compared to an HV of 9.78 cm/yr for somatropin (0.24 mg/kg/wk) in pGHD [9]. The Japanese phase III trial reported a higher HV for somatrogon (9.65 cm/yr) compared to 7.87 cm/yr for somatropin (0.175 mg/kg/wk) [10]. An extension study demonstrated an improvement in height standard deviation score (SDS) from -3.98 to -0.69 after 4 years of somatrogon treatment in pGHD patients [11]. Despite a higher prevalence of injection site pain compared to conventional treatment, a crossover phase III trial reported significantly lower life interference scores (8.63) after switching to somatrogon, compared to previous scores of 24.13 during somatropin treatment [12].

These clinical trials have demonstrated that somatrogon achieves comparable results in key clinical endpoints, including growth-promoting effectiveness, safety, and tolerability, while offering the advantage of once-weekly administration [8-12]. This suggests that treatment efficacy is maintained while improving patient convenience, thereby increasing its potential for practical use in clinical settings.

Although the efficacy and safety profile of somatrogon appears promising, Insulin like growth factor 1 (IGF-1) levels fluctuate over time, necessitating standardized monitoring. Measuring IGF-1 levels on day 4 postadministration is essential for assessing the efficacy and safety of somatrogon [5-7].

The long-term effects of somatrogon, particularly in comparison to daily somatropin, require further investigation to assess both efficacy and potential safety concerns over prolonged use. Answering these questions will require large-scale cohort surveillance studies, similar to the Kabi International Growth Study [13], the Genetics and Neuroendocrinology of Short Stature International Study [14], and the LG Growth Study in Korea [15].

Maniatis et al. [7] reviewed recent clinical trials evaluating somatrogon for pGHD, demonstrating its noninferior outcomes in height SDS, IGF-1 SDS, and safety compared to daily GH therapy.

This once-weekly formulation offers a viable alternative to daily treatment while significantly alleviating the burden of frequent injections for both patients and caregivers. As technological advancements continue, long-acting formulations with extended half-life are expected to revolutionize treatment approaches across various pediatric endocrinologic and metabolic disorders, paving the way for more patient-centered and personalized care. However, long-term safety and efficacy must be evaluated through large-scale cohort studies to ensure the optimal integration of these therapies into clinical practice.