INTRODUCTION: Glucagon-like peptide-1 receptor agonists are widely prescribed for diabetes and obesity. The association between GLP-1 RAs and thrombotic events remains unclear, with conflicting evidence from clinical and experimental studies. This study aims to assess the reporting of thrombotic adverse events with GLP-1 RAs in the FDA Adverse Event Reporting System (FAERS).
METHODS: A retrospective pharmacovigilance analysis of FAERS reports was performed. Thrombotic adverse events were identified using Standardized MedDRA Queries. Disproportionality was assessed via Reporting Odds Ratios. Time-to-onset was analyzed, and comparative analyses were conducted with Orlistat and SGLT2i.
RESULTS: 1,618 unique thrombotic AE reports involving GLP-1 RAs were identified. Arterial events predominated (55.3%), followed by venous (23.2%) and mixed events (21.5%). Compared with all other drugs, GLP-1 RAs were not disproportionately associated with thrombotic AEs (overall ROR = 0.67, 95% CI: 0.64-0.71). Venous events showed the lowest disproportionality (ROR = 0.53, 95% CI: 0.48-0.59). Liraglutide displayed higher RORs than other GLP-1 RAs, while tirzepatide showed the lowest. Compared with Orlistat, GLP-1 RAs had markedly lower odds of venous events (OR 0.27), and, versus SGLT2i, lower odds across all event types.
DISCUSSION: In this large FAERS analysis, GLP-1 RAs did not show a disproportionate reporting signal for thrombotic events and, in several comparisons, appeared to have lower thrombotic reporting than alternative agents. While limitations of spontaneous reporting preclude causal inference, these findings provide reassuring real-world safety data.
CONCLUSION: GLP-1 RAs were not associated with thrombotic AEs in FAERS and may confer a protective profile. Continued post-marketing surveillance is warranted.
