Evaluation of Semaglutide on Metabolic State in Prediabetic or Diabetic Schizophrenia Patients Under Clozapine or Olanzapine Treatment

The primary objective of this study is to evaluate the long-term effects of the **glucagon-like peptide-1 receptor agonist** semaglutide, administered once weekly, compared to a placebo, on the metabolic state of prediabetic or diabetic patients with **schizophrenia**. These patients, aged 18 to 65 years, have initiated treatment with the antipsychotic medications clozapine or olanzapine. The clinical relevance of this study lies in its potential to address the metabolic complications often associated with antipsychotic treatment in this patient population, which can exacerbate pre-existing metabolic disorders and impact overall health outcomes.

The clinical trial focuses on individuals diagnosed with **schizophrenia** who are aged between 18 and 65 years. The study population includes both male and female participants who have initiated treatment with clozapine or olanzapine within the last 60 months. Participants are required to have a diagnosis of prediabetes or type 2 diabetes, with specific plasma levels confirming their condition. The trial does not involve a vulnerable population. The sponsor has not provided information regarding the total number of participants. The study aims to assess the long-term effects of semaglutide, administered once weekly, compared to a placebo, on the metabolic state of these individuals over a period of 26 weeks. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the long-term effects of **semaglutide**, a glucagon-like peptide-1 receptor agonist, on the metabolic state of prediabetic or diabetic patients with schizophrenia who are undergoing treatment with the antipsychotic medications clozapine or olanzapine. This study is a randomized, double-blind, placebo-controlled trial, conducted over a period of 26 weeks. Participants will be randomly assigned to receive either semaglutide or a placebo, administered once weekly via subcutaneous injection. The primary endpoint of the trial is the change from baseline in glycated hemoglobin A1c (HbA1c), with secondary endpoints including changes in body weight, waist and hip circumference, blood pressure, heart rate, and various metabolic and psychological parameters.

The trial will commence with an inclusion (screening) visit, where eligibility criteria will be assessed, including confirmation of prediabetes or type 2 diabetes diagnosis and current treatment with clozapine or olanzapine. Participants will then be enrolled and randomized into the treatment or placebo group. Follow-up visits will occur at regular intervals throughout the study to monitor safety, adherence, and efficacy outcomes. These visits will include assessments of metabolic parameters, vital signs, and other relevant health indicators. The end-of-study visit will involve a comprehensive evaluation of all primary and secondary endpoints.

Participant involvement is expected to last for the entire 26-week duration of the trial, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with study procedures. The trial aims to provide valuable insights into the potential of semaglutide to mitigate metabolic side effects associated with antipsychotic treatment in this patient population.

The clinical trial involves the administration of **semaglutide**, marketed under the name Ozempic, which is provided as a **solution for injection** in a pre-filled pen. The pharmaceutical form is specifically designed for **subcutaneous injection**. The dosage is set at 1 mg per milliliter, with a maximum daily dose of 1 mg. The treatment is administered once weekly over a period of 26 weeks. The active substance, semaglutide, is a protein-based compound developed by Novo Nordisk A/S. The trial aims to assess the long-term effects of semaglutide on the metabolic state of prediabetic or diabetic patients with schizophrenia who are undergoing treatment with antipsychotic medications such as clozapine or olanzapine.

A **placebo** is also utilized in this study, serving as a comparator to the active treatment. The placebo is designed to mimic the administration of semaglutide, ensuring that the study maintains its double-blind nature. The placebo is referred to as "Placebo for semaglutide, CompCart 1.5 ml, PDS290." It is important to note that the placebo does not contain any active pharmaceutical ingredients and is used to evaluate the efficacy and safety of semaglutide by providing a baseline for comparison. The administration schedule for the placebo mirrors that of the active treatment, with once-weekly injections over the same 26-week period.

Efficacy in this clinical trial will be assessed by evaluating the impact of **semaglutide** on the metabolic state of prediabetic or diabetic patients with schizophrenia who are treated with clozapine or olanzapine. The primary endpoint for efficacy assessment is the change from baseline in glycated hemoglobin A1c (HbA1c) levels. Secondary endpoints include changes in body weight, hip and waist circumference, blood pressure, heart rate, plasma insulin, C-peptide, glucagon, incretin hormones, lipid profile, proteomics, bone markers, insulin sensitivity, beta-cell function (evaluated by HOMA), body composition and bone density (evaluated by DXA-scan), liver function (transaminases), liver fibrosis (FIB-4 score), and lifestyle factors such as alcohol, tobacco, and drug use, preference for sweet and fatty candy, psychopathology, activity, and quality of life.

The trial is designed to measure these parameters over a 26-week period, with semaglutide or placebo administered once weekly. The collection and analysis of these efficacy parameters will be conducted using validated laboratory tests and patient-reported outcomes. The trial aims to determine whether semaglutide can prevent the deterioration of metabolic state in the specified patient population, thereby addressing the metabolic side effects associated with antipsychotic treatment.