Heald Adrian H, Reynolds Gavin, Nash Isabel, Boyle Onagh, Daly Chris, Longson Damien, O'Shea Donal, Ingram Joseph, Holt Richard, Firth Joseph, Stedman Mike, Syed Akheel, de Hert Marc
University of Manchester, Manchester, UK.
Salford Royal Hospital, Salford, UK.
Adv Ther. 2025 Jun 19. doi: 10.1007/s12325-025-03261-0.
Weight gain has come to define the life experience of many individuals with schizophrenia and other severe enduring mental illnesses (SMI). In this clinical intervention study, we aimed to determine whether weekly treatment with the glucagon-like peptide-1 (GLP-1) agonist, semaglutide, as part of usual care, is feasible and acceptable to individuals in a psychiatric inpatient setting.
Fifteen inpatients (11 men/4 women) in a secure care environment, diagnosed with schizophrenia or schizoaffective disorder and with body mass index (BMI) of at least 30 kg/m were commenced on weekly subcutaneous semaglutide as per standard of care. BMI and glycated haemoglobin (HbA1c) were measured at baseline and monthly follow-up to 6 months, and quality of life (QOL) was surveyed at baseline and 6 months. Analysis was based on intention-to-treat.
Mean age of patients was 37 years (range 23-63). Time since diagnosis varied from 2 to 25 years. Mean initial BMI was 48.7 kg/m for women and 37.2 kg/m for men. Duration of semaglutide treatment ranged from 2-6 months. EuroQol 5-Dimensional Questionnaire, 5-Level Version Visual Analogue Scale (EQ5D5L QOL VAS) showed a mean improvement of + 7.5 (from 60 to 67.5) points. Improvement in QOL was overall significantly greater in those who remained on semaglutide (+ 9.5) than those who discontinued. Six patients discontinued semaglutide before the study end, including two who were discharged and no longer able to receive the intervention, and four who withdrew due to medical concerns. Individual percentage weight change varied from + 1 to - 12% (median 5%), and weight reduction was seen in all except two patients. All but one patient demonstrated a reduction in HbA1c levels. Mean HbA1c fell significantly from 41 (range 34-47) mmol/mol to 35.3 (31-45) mmol/mol. Importantly, all patients with baseline HbA1c in the non-diabetic hyperglycaemia range (42-47 mmol/mol) demonstrated a reduction of HbA1c to below 42 mmol/mol by 3 months. Prior to initiation of semaglutide, mean blood pressure was 127 (range 117-145) mmHg systolic and 82 (62-99) mmHg diastolic. At last assessment, average blood pressure was reduced to 121 (107-136) mmHg systolic and 79 (65-96) mmHg diastolic.
In this feasibility study, weekly semaglutide treatment was associated with improvement in self-rated overall QOL and reductions in BMI, HbA1c and blood pressure at up to 6 months follow-up. Even in patients who discontinued treatment before 6 months, initial benefits of weight reduction and improved QOL were still demonstrated. Further evaluation, including health economic assessment and longer-term follow up, may support the expanded use of GLP-1 agonists in improving the cardiometabolic profile and longitudinal health outcomes in individuals with SMI.
体重增加已成为许多精神分裂症患者和其他严重持久性精神疾病（SMI）患者生活经历的特征。在这项临床干预研究中，我们旨在确定将胰高血糖素样肽 -1（GLP-1）激动剂司美格鲁肽作为常规治疗的一部分进行每周一次治疗，在精神科住院环境中对患者是否可行且可接受。
在安全护理环境中的15名住院患者（11名男性/4名女性），被诊断为精神分裂症或分裂情感性障碍，体重指数（BMI）至少为30kg/m²，按照护理标准开始每周皮下注射司美格鲁肽。在基线和每月随访直至6个月时测量BMI和糖化血红蛋白（HbA1c），并在基线和6个月时调查生活质量（QOL）。分析基于意向性治疗。
患者的平均年龄为37岁（范围23 - 63岁）。确诊后的时间从2年到25年不等。女性的平均初始BMI为48.7kg/m²，男性为37.2kg/m²。司美格鲁肽治疗持续时间为2 - 6个月。欧洲五维健康量表5级视觉模拟量表（EQ5D5L QOL VAS）显示平均改善了 +7.5（从60到67.5）分。继续使用司美格鲁肽的患者（+9.5）的生活质量改善总体上显著大于停药患者。6名患者在研究结束前停用了司美格鲁肽，其中2名出院后无法再接受干预，4名因医疗问题退出。个体体重变化百分比从 +1%到 -12%不等（中位数为5%），除2名患者外均出现体重减轻。除1名患者外，所有患者的HbA1c水平均有所降低。平均HbA1c从41（范围34 - 47）mmol/mol显著降至35.3（31 - 45）mmol/mol。重要的是，所有基线HbA1c处于非糖尿病性高血糖范围（42 - 47mmol/mol） 的患者在3个月时HbA1c均降至42mmol/mol以下。在开始使用司美格鲁肽之前，平均血压收缩压为127（范围117 - 145）mmHg，舒张压为82（62 - 99）mmHg。在最后一次评估时，平均血压降至收缩压121（107 - 136）mmHg，舒张压79（65 - 96）mmHg。
在这项可行性研究中，每周一次的司美格鲁肽治疗与自我评定的总体生活质量改善以及在长达6个月的随访中BMI、HbA1c和血压降低相关。即使在6个月前停药的患者中，仍显示出体重减轻和生活质量改善的初始益处。进一步评估，包括健康经济评估和长期随访，可能支持扩大使用GLP-1激动剂来改善SMI患者的心脏代谢状况和长期健康结局。
