SUN-706 - Metabolic Rescue in Schizophrenia Spectrum Disorders: GLP-1 Receptor Agonists for Antipsychotic-Induced Weight Gain

Introduction

Antipsychotic-induced weight gain (AIWG) is the most common reason for reduced treatment compliance in patients with schizophrenia spectrum disorders and contributes to increased cardiometabolic morbidity. Glucagon-like peptide-1 (GLP-1) receptor agonists have demonstrated metabolic benefits in the general population, with emerging evidence supporting their use in antipsychotic-treated patients. This systematic review and meta-analysis evaluated the efficacy of GLP-1 receptor agonists as a targeted intervention for weight and glycaemic outcomes in patients with schizophrenia spectrum disorders.

Methods

We conducted a systematic review in accordance with PRISMA guidelines, searching PubMed, Scopus, Web of Science, and Embase from inception to December 2025. Randomised controlled trials (RCTs) evaluating the effectiveness of GLP-1 receptor agonists in patients receiving antipsychotic treatment were included. Primary outcomes were changes in body weight and body mass index (BMI), while secondary outcomes included HbA1c and insulin levels. Data were analysed using random-effects models to account for between-study variability. Continuous outcomes were pooled as mean differences (MDs) using the generic inverse variance method, and dichotomous outcomes were summarised as risk ratios (RRs). Heterogeneity was assessed using the I² statistic. All statistical analyses were performed using Review Manager (RevMan) version 5.4.

Results

From 4,351 initial citations, six RCTs met the inclusion criteria. Among patients with schizophrenia receiving antipsychotic medications, treatment with GLP-1 receptor agonists resulted in significant reductions in body weight (MD = −5.07 kg, 95% CI: −7.03 to −3.12, P < 0.00001) and BMI (MD = −1.63 kg/m², 95% CI: −2.29 to −0.96, P < 0.00001) compared with placebo. No significant reductions were observed in HbA1c (MD = −0.13%, 95% CI: −0.40 to 0.14, P = 0.34) or insulin levels (MD = −0.13 µIU/mL, 95% CI: −0.62 to 0.36, P = 0.59), reflecting predominantly euglycaemic (non-diabetic) study populations with maintained glucose homeostasis.

Conclusion

GLP-1 receptor agonists demonstrate significant efficacy in reversing AIWG, achieving a mean weight loss of approximately 5 kg. The absence of significant reductions in HbA1c or insulin levels suggests a favourable safety profile in non-diabetic patients, with a low risk of hypoglycaemia. These findings support the integration of GLP-1 receptor agonists into the management of AIWG to mitigate metabolic risk.

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