OBJECTIVES: In recent years, GLP-1 receptor agonists (GLP-1 RAs) have revolutionized the management of type 2 diabetes mellitus (T2DM) and obesity, becoming essential for their effectiveness in glycemic control and weight loss. However, concerns about potential psychiatric side effects, particularly suicidal ideation, have prompted significant debate and alerts from the EMA and FDA. This meta-analysis aims to systematically evaluate and synthesize evidence on the association between GLP-1 RAs and suicidal ideation in T2DM and obesity patients, addressing the potential risks linked to these widely used medications.

METHODS: We conducted a literature/systematic search of PubMed, Embase, and Scopus from 2018 to the present to identify observational studies examining the relationship between GLP-1 RAs and suicidal ideation. Studies reporting odds ratios (OR), relative risks (RR), or hazard ratios (HR) for suicidal ideation in patients using GLP-1 RAs were included. Additionally, to address the contradictory results in the literature, we included observational studies using reporting odds ratios (ROR) for adverse event reporting separately. RRs, RORs, and 95% confidence intervals (CIs) comparing underweight, overweight, and obese groups with normal weight were pooled using random effects models.

RESULTS: In total, 5 studies involving 746,306 patients with suicidal ideation were included in the meta-analysis of RRs. Compared with patients using insulin, metformin, or orlistat, those using GLP-1 RAs had a non-significant decreased risk for suicidal ideation (RR = 0.83, 95% CI, 0.73-1.03, p = 0.06). Underweight patients had a significantly increased risk for total suicidal injury (RR = 1.05, 95% CI, 1.02-1.07, p < 0.03). A similar, but not significant, association of ROR for suicidal ideation events with GLP-1 RA use was also observed.

CONCLUSIONS: GLP-1 RA use shows a non-significant decrease in suicidal ideation risk compared to insulin, metformin, or orlistat, warranting further research to confirm these findings.