Impacts of Glucagon-like Peptide-1 Receptor-Agonist (GLP-1 RA) Treatment for Metabolic Disturbances and Weight Gain in Patients on Clozapine/Olanzapine: A Systematic Review

Clozapine and olanzapine are important medications in the management of psychiatric conditions such as schizophrenia. However, metabolic disturbances and weight gain are common side effects of these drugs. We aimed to evaluate the effects of GLP-1 RAs treatment for metabolic disturbances and weight gain in patients on clozapine/olanzapine. For this systematic review, searches were conducted in eight different databases. After screening, outcome data was synthesized regarding weight gain and biochemical and clinical indicators of metabolic disturbance, as well as for adverse events/side effects, and any other benefits of GLP-1 RA treatment. A total of 14 studies were included in this medical systematic review, of which four were unique randomized control trials (RCTs), with study contexts including Australia and Denmark. GLP-1 RAs that were utilized include semaglutide, exenatide, and liraglutide. It was consistently demonstrated across studies that, when followed-up, those on GLP-1 RAs had achieved statistically lower levels of weight gain compared to those receiving placebo. A similar effect was seen on fasting glucose levels and glycated haemoglobin levels. Effects on other metabolic parameters were inconsistent. There were minimal gastrointestinal, psychological, cardiac, and other side effects noted across studies. GLP-1 RAs may offer utility in addressing the metabolic side effects of olanzapine/clozapine, but further research is needed. There remains a need to better understand impacts and potential side effects in larger and more diverse populations, as well as a need to better evaluate the long-term outcomes for patients.