GLP-1 Receptor Agonists Show No Disproportionate Thrombotic Event Reporting in Large FAERS Analysis
Background
The widespread use of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) for type 2 diabetes and obesity has raised questions about their full safety profile. While these agents offer significant cardiometabolic benefits, the association between GLP-1 RAs and thrombotic events—a critical concern in these patient populations—remains unclear due to conflicting evidence. Understanding real-world safety data is crucial to inform clinical practice and patient counseling, especially given the high baseline cardiovascular risk in individuals with these conditions.
Study Design
Researchers conducted a retrospective pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database, spanning reports from 2020 to 2025. They identified thrombotic adverse events (AEs) associated with GLP-1 RAs using Standardized MedDRA Queries. Disproportionality was assessed via Reporting Odds Ratios (RORs) to compare GLP-1 RA reports against all other drugs in the database. Comparative analyses were also performed against Orlistat and SGLT2 inhibitors to provide context for the observed reporting patterns.
Results
The analysis identified 1,618 unique thrombotic AE reports involving GLP-1 RAs. Arterial events constituted the majority at 55.3%, followed by venous events at 23.2%, and mixed events at 21.5%. Compared to all other drugs in FAERS, GLP-1 RAs were not disproportionately associated with thrombotic AEs, showing an overall ROR of 0.67 (95% CI: 0.64-0.71). Venous events exhibited the lowest disproportionality, with an ROR of 0.53 (95% CI: 0.48-0.59).
Key Findings
- 1,618 unique thrombotic AE reports linked to GLP-1 RAs were identified in FAERS.
- GLP-1 RAs were not disproportionately associated with thrombotic AEs overall (ROR = 0.67, 95% CI: 0.64-0.71).
- Venous thrombotic events showed the lowest disproportionality (ROR = 0.53, 95% CI: 0.48-0.59).
- Compared to Orlistat, GLP-1 RAs had markedly lower odds of venous events (OR 0.27).
- Compared to SGLT2 inhibitors, GLP-1 RAs showed lower odds across all thrombotic event types.
Why It Matters
This large-scale pharmacovigilance study provides reassuring real-world safety data for GLP-1 RAs, suggesting they do not carry a disproportionate risk of thrombotic events. This finding reinforces the favorable safety profile of GLP-1 RAs, particularly for individuals managing type 2 diabetes and obesity, who often have elevated cardiovascular risk. The data may even suggest a protective profile, which could influence prescribing patterns and patient confidence. While spontaneous reporting limitations prevent causal inference, these results contribute significantly to the ongoing assessment of GLP-1 RA safety, supporting their continued use as foundational therapies.
glp-1-ras
pharmacovigilance
thrombotic-events
faers
safety
type-2-diabetes