Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Individuals with schizophrenia spectrum disorders (SSD) experience a vast range of health complications; 50% of patients fall obese category, with a 3-5-fold greater rate of type 2 diabetes than the general population. Antipsychotic (AP) medications are the main-stay treatment in SSDs, but unfortunately cause drastic weight gain, worsened blood glucose (BG), and other health complications. As a result, there is an incredibly high rate of cardiovascular disease and early mortality in this population. Metformin, a common treatment for type 2 diabetes in the general population, is recommended as a first line treatment to address these AP related side effects. However, only 1 in 4 individuals taking APs experience weight loss with metformin with no clear guidelines in place for the subset of individuals who don't respond to metformin. Semaglutide is a newer weekly injectable weight loss medication belonging to a class of drugs called glucagon like peptide-1 receptor agonists (GLP-1RA). It has impressive weight loss properties in the general population. However, its safety and efficacy in people with SSDs who don't respond to metformin is not known. Our study aims to investigate the effectiveness of semaglutide to treat obesity and other metabolic factors in individuals with SSD that did not respond to metformin. This study will test semaglutide compared to placebo. We will recruit patients with SSD and obesity that failed to see significant weight loss after taking metformin. Participants will be randomly assigned to semaglutide or placebo treatment. They will not know which group they are assigned to. The duration of treatment will be 32 weeks, where we will conduct frequent visits to test for body weight, BG metabolism, MRI scans to measure body fat changes, and assessments of brain health. If successful, this alternative route could vastly improve both the health burden, quality of life, and treatment adherence of this population.