Treatment of clozapine associated obesity and diabetes with exenatide in people with schizophrenia

INTERVENTION: Participants will be assigned to Arm 1 or Arm 2 depending on their clinical diagnosis and then randomised to the control or intervention group. Arm 1: clozapine‐treated people with Type 2 Diabetes Mellitus (T2DM). Intervention group: once weekly exenatide subcutaneous injection (2mg) delivered by a mental health or trial nurse for 24 weeks. Exenatide will be administered in addition to current glucose lowering agents. Note: For participants in the intervention group who are already on a sulfonylurea (SU) and have a HbA1c equal to or below 7.5%, their SU will be ceased to avoid hypoglycaemia. If the participant's HbA1c is between 7.5% and 8.5%, the dosage of the SU will be halved to avoid hypoglycemia. For participants in the intervention group who are on a SU and have a HbA1c of >8.5% the dose of the SU will be maintained. Control group: treatment as usual; no placebo Arm 2: clozapine‐treated obese people (BMI greater than or equal to 30kg/m2) without diabetes. Intervention group: once weekly exenatide subcutaneous injection (2mg) delivered by a mental health or trial nurse for 24 weeks. Exenatide will be administered in addition to current glucose lowering agents. Control group: treatment as usual; no placebo CONDITION: Treatment resistant schizophrenia diabetes obesity PRIMARY OUTCOME: Acceptability as assessed by a patient‐reported outcome questionnaire (designed specifically for this study). Weight loss for subjects in Arm 1, as measured by the proportion of people with >5% weight loss. Weight loss for subjects in Arm 2, as measured by the proportion of people with >5% weight loss. SECONDARY OUTCOME: Change in insulin sensitivity as determined by homeostatic model assessment (HOMA) Change in metabolic markers from baseline Change in symptoms of psychosis, as measured by the Brief Psychiatric Rating Scale‐Anchored (BPRS‐A) score Primary Outcome: Tolerability as measured by adverse event reports and study dropout rates. ; ; Known adverse events of exenatide include transient gastrointestinal side effects (nausea, vomiting, diarrhoea), injection site reactions (redness, itchiness, haematoma), dyspepsia and hypoglycaemia (mainly when used with a sulphonylurea or insulin). Rarely, altered renal function and pancreatitis have been reported. INCLUSION CRITERIA: Provision of informed consent prior to any study specific procedures Clinical diagnosis of Schizophrenia or Schizoaffective Disorder On oral clozapine for at least 18 weeks Stable body weight (defined as less than 5kg change in weight over the past 3 months before inclusion) For Arm A a) Diagnosis of Type II Diabetes Mellitus b) Current and stable therapeutic doses of oral glucose lowering agents for 3 months prior to recruitment c) BMI greater than or equal to 30kg/m2 and less than 45kg/m2 For Arm B a) BMI greater than or equal to 30kg/m2 and less than 45kg/m2