Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Psychiatric Disorders: A Systematic Review...

To explore the association of GLP-1 receptor agonists (GLP-1 RAs) with the risk of psychiatric disorders.

A systematic search was performed in PubMed, EMBASE, Cochrane Library and Web of Science (inception to June 13, 2025). Randomised clinical trials (RCTs) that compared the use of GLP-1 RAs with either placebo or other non-GLP-1 RAs treatments were included. Psychiatric disorders were collected based on reported treatment-emergent adverse events. Following PRISMA guidelines, two reviewers independently extracted data and evaluated the quality of each study using the Cochrane tool. Evidence quality was assessed using the GRADE framework.

A total of 133 378 participants were included across 86 RCTs. No significant statistical difference was found in the incidence of psychiatric disorders between the GLP-1 RAs group and the control group (RR, 0.96; 95% CI, 0.85-1.08; I² = 0%; ARD, -9 per 10 000 persons/year). GLP-1 RAs treatment was not associated with depression (RR, 0.88; 95% CI, 0.70-1.10), suicide (RR, 0.90; 95% CI, 0.59-1.38), anxiety (RR, 0.92; 95% CI, 0.72-1.19), sleep disorder (RR, 0.98; 95% CI, 0.70-1.37), bipolar disorder (RR, 1.19; 95% CI, 0.56-2.55), delirium (RR, 1.11; 95% CI, 0.74-1.66), addictive disorder (RR, 0.89; 95% CI, 0.45-1.77) or schizophrenia (RR, 1.45; 95% CI, 0.61-3.47). No statistically significant associations were observed for drug type, indication, dose, treatment duration, comparator type, baseline BMI, trial designation, age, inclusion of baseline psychiatric disorders or reporting category. Meta-regression analyses revealed no significant effect of changes in fasting blood glucose, haemoglobin A1c, weight or BMI on the risk of psychiatric disorders.

GLP-1 RAs use was not associated with the risk of psychiatric disorders, including depression, suicide or anxiety.

PROSPERO Identifier: CRD42024546896.