The effect of semaglutide with lifestyle intervention on the physical health of antipsychotic drug-treated patients in a secure mental health setting: the STEP@STAH pilot study protocol for uncontrolled pre-post intervention study

<p dir="ltr"><b>Background:</b> Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic drug treatment, particularly with second generation medications such as clozapine and olanzapine. Weight gain in patients undergoing antipsychotic therapies is a significant concern, often compounded by factors related to their condition that can be particularly challenging in a secure care setting. While there is significant evidence to support the benefit of semaglutide, one of the available glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to promote weight loss for those who have a general weight-related health issue and meet the referral criteria for specialist services, it is unclear whether it will be as successful in people who have specifically gained weight due to medication-associated side effects and who reside in a secure care setting.</p><p dir="ltr"><b>Objectives:</b> To assess the impact of semaglutide in combination with a lifestyle behavioural change intervention on the physical health measures of patients in a secure setting who have atypical AIWG and to identify enhancements to the intervention, specifically geared towards improving its acceptability and adherence from both staff and patients' perspectives.</p><p dir="ltr"><b>Methods:</b> This two-year uncontrolled pre-post pilot study aims to recruit 20 in-patient participants. Adult patients of any diabetic status with a minimum BMI of 35.0kg/m2 or a BMI of 32.5 kg/m2 for people from South Asian, Chinese, other Asian, Middle Eastern, Black African or African-Caribbean family, who are receiving inpatient treatment and are treated with either olanzapine or clozapine will be eligible for inclusion in the study. Patients will receive semaglutide (Wegovy) at a maintenance dose of 2.4mg once a week for 2 years. All participants will also receive a lifestyle behavioural change intervention.</p><p dir="ltr"><b>Results:</b> Findings will reveal whether the format of the interventional approach is both sustainable and effective for adult patients diagnosed with severe mental illness and living with obesity, who are currently residing in a secure mental health setting. Implementation changes that could improve the acceptability and adherence to the intervention will be explored.</p><p dir="ltr"><b>Conclusion:</b> This research should be beneficial for patients with psychosis who are living with obesity and are residing in a secure setting, as the findings of the study may ultimately reduce the mortality risk in this patient group.</p><p dir="ltr"><b>Trial registration:</b> The study has been registered on 20/12/2024 as a clinical trial on the US Clinical Trials Registry ClinicalTrials.Gov (NCT06754163).</p>