Effect of Glucagon-like Peptide-1 Receptor Agonists on Cardio-Metabolic Risk Factors among Obese/Overweight Individuals Treated with Antipsychotic Drug Classes: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) constitute a drug class primarily developed for the treatment of subjects with type 2 diabetes, although they have also provided significant benefit for subjects with obesity without underlying diabetes. Individuals with psychotic disorders who are receiving antipsychotic treatment are a patient population at risk of developing obesity, which is linked to other metabolic disturbances. Methods: We searched PubMed and the Cochrane Library from inception to 1 December 2022, for randomized controlled trials (RCTs) enrolling obese or overweight adult subjects with an underlying psychotic disorder treated with antipsychotic drugs, randomized either to GLP-1RAs or a control. We set as the primary efficacy outcome the change in body weight and as secondary efficacy outcomes the change in body mass index (BMI) and in waist circumference, along with indices of glycemia, lipid profile, and blood pressure. Results: We pooled data from 4 trials (2 with liraglutide and 2 with exenatide) in a total of 199 enrolled subjects. GLP-1RA treatment, compared to control, resulted in a significant decrease in body weight by 3.8 kg [mean difference (MD) = −3.80, 95% CI; −6.35 to −1.24, I² = 64%]. In addition, GLP-1RA treatment led to a significant decrease in BMI, compared to control, of 1.04 kg/m² (MD = −1.04, 95% CI; −1.92 to −0.17, I² = 35%). However, no significant effect on waist circumference was shown (MD = −3.2, 95% CI; −6.47 to 0.08, I² = 88%). A significant improvement in glycemia and lipid profiles was also demonstrated with GLP-1RAs. No subgroup difference between liraglutide and exenatide was shown, and the use of GLP-1RAs did not increase the risk for treatment discontinuation compared to the control group. Conclusion: Treatment with GLP-1RAs can significantly improve weight loss and other cardiometabolic risk factors in obese people taking antipsychotic medications.