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

ABSTRACT 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 2 = 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 2 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.