Obesity and Schizophrenia: Results of a Feasibility Study with Semaglutide to Assist Weight Loss

Introduction: 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. Methods: 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/m² 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. Results: 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/m² for women and 37.2 kg/m² 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. Conclusion: 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.