Efficacy and safety of GLP-1 receptor agonists for metabolic outcomes in patients with schizophrenia spectrum disorders treated with second-generation antipsychotics: a systematic review and meta-analysis

Schizophrenia is a serious psychiatric disorder which, in addition to a general deterioration in quality of life, can reduce life expectancy by up to 15 years. Patients suffering from schizophrenia spectrum disorders are at increased risk of cardiovascular and metabolic diseases. In addition, due to their illness, the diagnosis of these health problems is difficult, and treatment is delayed. What is more, standard antipsychotic therapy with second generation antipsychotics (SGAs) further increases body weight and cardiovascular and metabolic problems, and the most effective drug in this group, clozapine, is also associated with the highest risk of these complications. In fact, SGAs are suspected of inhibiting the production of glucagon-like peptide 1 (GLP-1), which is a key agent in glucose homeostasis. Therefore, GLP-1 receptor agonists (GLP-1 RAs) appear to be a promising additional form of therapy for patients suffering from schizophrenia spectrum disorders. In previous years, a small number of clinical studies and systematic reviews have confirmed the effectiveness of this form of therapy, but since then, new RCTs have emerged that may significantly influence the results of the synthesized data and increase their value. The aim of this project is to conduct a systematic review and meta-analysis to provide an updated and comprehensive synthesis of available evidence regarding efficacy and safety of GPL-1 RAs in patients suffering from schizophrenia spectrum disorders treated with SGAs. This review will focus on randomized double-blind controlled trials (RCTs) comparing patients with schizophrenia spectrum disorders on SGAs treated with GLP-1 RAs to control group receiving placebo. Outcomes of interests include changes in anthropomethric parameters - bodyweight, BMI, waist circumference, waist to hip ratio, systolic and diasystolic blood pressure; glycaemic parameters - glycated haemoglobin (HbA1c), fasting blood glucose (FBG); metabolic parameters - high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), body fat, total fat mass; Safety - occurence of adverse events. Data will be synthesized using random-effects models, and where possible sensitivity and subgroup analyses will be performed. Based on current hypotheses we expect that GLP-1 RAs will significantly reduce anthropomethric, glyceamic and metabolic parametres. The significance of this project lies in its potential to synthesise the previous results, newly emerged evidence and draw the most up-to-date and reliable conclusions.