Abstract
BACKGROUND: Inconclusive findings regarding the association between suicidal ideation/suicide attempt and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been recently revealed in a small number of studies. METHODS: This was a multinational self-controlled case series analysis using Hong Kong's Clinical Data Analysis and Reporting System (2008-2023), Taiwan's National Health Insurance Research Database (2012-2020) and the UK's IQVIA Medical Research Database with The Health Improvement Network (2000-2021). A total of 642 suicide attempt or self-harm cases with GLP-1RA use were included to assess pooled incident rate ratios (IRRs) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment with their 95% CIs. RESULTS: The pooled IRR (95% CI) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment was 0.67 (0.51 to 0.88). The suicide attempt or self-harm risk varied with the time window of GLP-1RA use, with pooled IRRs (95% CIs) of 1.94 (0.86 to 4.37), 0.61 (0.23 to 1.63), 0.72 (0.37 to 1.41), 0.60 (0.32 to 1.09) and 0.63 (0.49 to 0.87) for the pretreatment period and Days 1-30, Days 31-90, Days 91-180 and Days>180 of GLP-1RA treatment, respectively. Subgroup analyses by age, sex and individual GLP-1RAs and sensitivity analyses showed no significant increase in the suicide attempt or self-harm risk associated with GLP-1RA use. The point estimate and CI of the E-value for suicide attempts or self-harm were 2.35 and 1.53, respectively. CONCLUSIONS: We found no increase in the risks of suicide attempts or self-harm following GLP-1RA treatment, and even in the long-term use of GLP-1RAs. Close monitoring of potential suicide attempts or self-harm and ensuring treatment tolerability during treatment initiation are required, and well-controlled or pragmatic trials remain warranted to validate our findings.