EFFECTS OF GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS (GLP-1RAS/GLP-1S) INTEGRATION IN PATIENTS UTILIZING ANTIPSYCHOTICS

Psychotropic medications, especially antipsychotics, such as olanzapine and clozapine, have been known to cause the most metabolic adverse effects in psychiatric patients. While lifestyle modifications are highly recommended as a first-line, they are not often followed by most psychiatric patients and so far metformin has been one of the most successful treatments to help reduce the antipsychotic-induced. More recently, glucagon-like peptide-1 receptor agonists (GLP-1/GLP-1RAs) have been on the rise in mitigating metabolic issues in psychiatric and other patient populations. This review utilized a primary literature search across key electronic databases and journals, including PubMed, Embase, and Google Scholar, to identify eligible articles for this review. Key inclusion criteria for this study focused on articles published within 10 years exploring glucagon-like peptide 1 receptor agonist use in patients with concurrent antipsychotic use. Search phrases included “glucagonlike peptide 1 receptor agonist (GLP-1/GLP-1RA) and schizophrenia”, “GLP-1 and antipsychotic use”, and/or “GLP-1 and olanzapine”, which yielded 14 studies that met the inclusion criteria. In 14 reviewed studies, GLP-1s have been shown to decrease weight and BMI in patients experiencing metabolic side effects from antipsychotic use without increasing psychiatric adverse effects. Two preclinical rodent trials found that GLP-1 receptor agonists reduced metabolic disturbances caused by antipsychotics and improved measures such as glucose tolerance and insulin sensitivity. Consistent with these findings, three studies in human populations receiving antipsychotic medications demonstrated significantly greater weight loss in GLP-1 adjunctive therapy groups compared to standard treatment alone. These randomized controlled trials and comparative studies have found that patients were more likely to experience a > 5% weight decrease in weight-loss trials and comparative studies have found that patients were more likely to experience a > 5% weight decrease compared to other methods or placebo groups. Additionally, two studies involving semaglutide demonstrated improvements in metabolic biomarkers beyond weight reduction. These studies reported significant reductions in HbA1c, fasting glucose, and insulin resistance, thereby demonstrating direct metabolic benefits independent of weight-loss effects. Across all reviewed studies, GLP-1 receptor agonists were well tolerated with gastrointestinal side effects being the most commonly reported adverse effect, and no evidence of worsening psychiatric symptoms. GLP-1s have been shown to effectively attenuate metabolic effects associated with antipsychotic use without causing any worsening mental health symptoms in these patients. Further research will be needed to investigate if GLP-1s will have caused any long-term issues in patients who have been on this for years, as well as physical and mental repercussions in the psychopharmacological setting.