Impact of GLP-1 Receptor Agonists on Suicide Behavior: A Meta-Analysis Based on Randomized Controlled Trials.

BACKGROUND: This meta-analysis aims to assess the association between exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and the incidence of suicidal behavior in patients with type 2 diabetes mellitus (T2DM)/obesity. METHODS: A comprehensive search of electronic databases, including PubMed, Web of Science, the Cochrane Library, and ClinicalTrials.gov, was conducted from the inception of the databases. The risk ratio (RR) and 95% confidence intervals (95% CI) were calculated. RESULTS: This meta-analysis included data from 25 randomized controlled trials (RCTs). The results indicated no significant difference in the incidence of suicidal behavior between the GLP-1 RA exposure group and the control group (RR = 0.84, 95% CI: 0.54-1.32, p = 0.46, I = 0%). Subgroup analysis showed no significant differences in the incidence of suicidal behavior among participants with T2DM (RR = 0.74), obesity (RR = 1.07), adolescents (RR = 0.91), and adults (RR = 0.84). Additionally, no significant differences were observed between the two groups in any type of suicidal behavior, including suicidal ideation (RR = 1.04), suicide attempts (RR = 0.68), depression-related suicides (RR = 0.65), and completed suicides (RR = 1.06). There were also no significant differences between the groups for any type of GLP-1 RA, including dulaglutide (RR = 0.46), exenatide (RR = 0.98), semaglutide (RR = 0.82), lixisenatide (RR = 1.25), and liraglutide (RR = 0.92). No significant differences were observed between the exposure group and control group according to different comparators, including placebo (RR = 0.91) and others (RR = 1.08). All subgroup analyses showed p-values greater than 0.05 (two-sided tests) and I values of 0%. CONCLUSION: Our findings suggest that there is no significant association between GLP-1 RA exposure and suicidal behaviors in patients with T2DM or obesity.