Efficacy and Safety of GLP-1 Receptor Agonists for the Management of Antipsychotic-Induced Weight Gain

Abstract

Objective:

The objective of this systematic review and meta-analysis was to compare the efficacy and safety of glucagon-like peptide-1 (GLP-1) receptor agonists for the management of antipsychotic-induced weight gain.

Data Sources:

A systematic review was conducted following PRISMA methodology through July 2025 that evaluated the efficacy and safety of GLP-1 agonists for the management of antipsychotic-induced weight gain.

Study Selection and Data Extraction:

Efficacy endpoints were change in body weight (kg), change in body mass index (BMI) (kg/m²), and change in HbA_1c (%). The safety endpoint was gastrointestinal (GI) adverse effects. A P-value of 0.05 was considered statistically significant, and heterogeneity was reported as I².

Data Synthesis:

Six studies were included in this systematic review, of which 4 trials were included in the meta-analysis. The difference found between GLP-1 agonists and placebo was a change in weight of −5.85 kg (P = 0.0622, 95% CI = −9.72 to −1.97), a change in BMI of −2.11 kg/m² (P = 0.7692, 95% CI = −5.51 to 1.29), and a change in HbA_1c of −1.58 (P = 0.6659, 95% CI = −4.75 to 1.58). The overall risk ratio for a patient to experience a GI-related adverse effect when taking a GLP-1 agonist compared to placebo was 1.83 (95% CI = 1.42 to 2.37).

Relevance to patient care and clinical practice:

While the efficacy endpoints did not reach significance, this meta-analysis shows that select GLP-1 receptor agonists may be used to promote weight loss in patients taking antipsychotics. Controlling antipsychotic-induced weight gain helps patients remain adherent to therapeutic doses of their antipsychotic medications.

Conclusion:

The use of certain GLP-1 agonists may be considered to help promote weight loss in patients experiencing antipsychotic-induced weight gain.