Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Psychiatric Disorders: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Diabetes Obes Metab. 2026 Mar 19. doi: 10.1111/dom.70692. Online ahead of print.

ABSTRACT

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

METHODS: 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.

RESULTS: 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.

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

TRIAL REGISTRATION: PROSPERO Identifier: CRD42024546896.

PMID:41852258 | DOI:10.1111/dom.70692