GLP-1R Agonists for Weight Loss in Psychiatric Disorders: A Systematic Review and Meta-analysis

Context Individuals with psychiatric disorders have a higher prevalence of obesity, partly because of the use of psychotropic medications. Safe and effective pharmacological interventions for weight management in this population are needed. Objective To assess the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1Ras) in individuals with psychiatric disorders and obesity/overweight through a systematic review and meta-analysis, focusing on weight and metabolic outcomes. Data Sources We searched PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov until May 2025 for observational studies that evaluated GLP-1RAs in this population. Study Selection Studies including adults with psychiatric disorders and obesity treated with GLP-1RAs were eligible; 10 randomized controlled trials met the inclusion criteria. Data Extraction Two reviewers independently extracted the data and assessed the risk of bias using the Cochrane RoB 2 tool. Outcomes included weight, body mass index (BMI), waist circumference, glucose level, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglycerides, and adverse events. Data Synthesis GLP-1RAs significantly reduced body weight [mean difference (MD) −5.03 kg; 95% confidence interval (CI): −6.04 to −4.01)], BMI (MD −1.59 kg/m²; 95% CI: −2 to −1.18), waist circumference (MD −3.4 cm 95% CI: −4.83 to−1.97), and fasting glucose (MD −0.29 mmol/L; 95% CI: −0.53 to −0.05) compared to controls. Gastrointestinal side effects were more frequent but generally mild and did not increase discontinuation rates. Conclusion GLP-1RAs are effective and well-tolerated for managing obesity in psychiatric populations, offering significant weight and metabolic benefits. Further studies are needed to evaluate newer agents, such as semaglutide and tirzepatide, particularly in longer trials with standardized protocols.