Study investigating whether the drug semaglutide could be a safe and effective way of reducing metabolic problems, such as a high Body Mass Index (BMI) and high blood sugar levels, in people with psychosis.

Brief name Study drug – Semaglutide subcutaneous administration Rationale People experiencing psychotic illnesses such as schizophrenia have a shortened life expectancy of 20 years compared to the general population. The biggest contributor to this premature mortality is the higher incidence of cardiometabolic disease, often associated with the initiation of antipsychotic medications (APM) used to treat symptoms of psychosis. Whilst the increased risk of cardiometabolic disease is often considered to be a result of obesity and weight gain from APMs, there is evidence that APM’s also disrupt the way glucose is metabolised. Semaglutide, a drug that influences glucose metabolism, is part of a class of drugs used in the treatment of diabetes to aid in weight loss. This study will examine the impact semaglutide has on metabolic risk factors in people with psychosis who are at risk of developing type 2 diabetes. Procedures Throughout the 24-week intervention participants in the intervention group will meet with the study nurse weekly to receive the study drug (semaglutide) and complete relevant measures. Dose Titration Phase (study weeks 1-8) During the first 8 weeks of participation dose escalation of semaglutide is required; this is the Dose Titration Phase. During weeks 1-4 of the Dose Titration Phase, a dose of 0.25mg semaglutide will be administered subcutaneously by the study nurse via a pen-injector each week. During weeks 5-8 of the Dose Titration Phase, a dose of 0.5mg semaglutide will be administered subcutaneously by the study nurse each week. Following successful completion of the Dose Titration Phase (end week 8), the Therapeutic Intervention Phase of the study will commence. Therapeutic Intervention Phase (study weeks 9-24) During the 16-week intervention phase, 1.0mg semaglutide will be administered subcutaneously each week via a pen-injector either self-administered or by the study nurse in those participants who prefer not to self-administer. Following completion of the Intervention Phase, semaglutide injections will be ceased. Mode of delivery All participants will be offered the opportunity to self-administer the study drug using the pen-injector from the start of the Therapeutic Intervention Phase, under the supervision of the study nurse. Those who prefer the nurse to administer the drug will continue to visit the outpatient clinic to receive their weekly dose. Participants who wish to self-administer will be offered the option to do so in person or whilst in a telehealth consultation with the study nurse who will monitor the correct dose setting and completion of administration. Attendance and administration will be recorded in the participant log to monitor intervention adherence. Location All study appointments will take place at a community mental health building, where participants usually attend for their routine appointments with their treating team. Sub-Study Participants in the sub-study will receive the same intervention as the main intervention group, however will complete additional measures including a DEXA body scan. Recruitment for the sub-study will be conducted sequentially from those who meet the criteria for inclusion in the intervention group. Recruitment to the sub-study will cease once 12 participants have been allocated or once there are no remaining participants of the main study to approach.