Abstract Disclosure: S. Fujio: None. R. Makino: None. J. Sugata: None. T. Hanada: None. R. Hanaya: None. Introduction: In Japan, the restriction on the administration of somapacitan, a long-acting growth hormone (GH) analogue, was lifted in December 2022, allowing the drug to be administered to many patients with severe growth hormone deficiency (sGHD). [Patients and methods] We have 10 patients for whom somapacitan was started as a new drug regime and 26 patients who switched from their daily GH replacement therapy. Among these 36 patients, 21 patients (5 new cases and 16 switched cases) who were followed for more than 6 months after the start of treatment were included in the present study. We compared lipid metabolism, glucose tolerance, liver function, and quality-of-life before and after treatment with somapacitan. [Result] The study population included 12 men and 9 women with a median age of 65 years. Cases included 15 NF-PitNET, 2 Lactotroph PitNET, 2 germ cell tumor, 1 craniopharyngioma, and 1 granuloma. Starting doses of somapacitan were 1.5 mg/week for adults to 60 years of age and 1.0 mg/week for patients aged >60 years. In the switched cases, the median levels of T-chol dropped from 214.5 to 198.5 mg (p<0.05). The median levels of HbA1c dropped from 5.9 to 5.8% (p<0.05). In the newly prescribed cases, the median levels of γ-GTP dramatically improved from 53 to 34I U/L, but this was not statistically significant. In the newly prescribed cases, quality-of-life assessment by Adult Hypopituitarism Questionnaire; AHQ showed improvement in both psychological/social aspects and physical function, but the number of cases was small and no significant difference was obtained. Body fat percentage measured by the impedance method showed no significant change in either the switched or newly prescribed groups. There were no adverse events, but some participants commented that it was easier to forget weekly injections of somapacitan than the daily GH. [Discussion] We were able to introduce somapacitan without any major problems. In newly prescribed cases, somapacitan resulted in a significant improvement in liver function. Improvements in lipid metabolism and glucose tolerance were observed in the switched patients. Compared to the daily GH replacement therapy, somapacitan may have a higher GH replacement effect. Presentation: 6/3/2024