Semaglutide shows lower thyroid cancer adverse event reporting odds compared to tirzepatide in pharmacovigilance data
Background
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized Type 2 Diabetes Mellitus (T2DM) management, offering significant benefits in glycemic control, weight reduction, and cardiovascular health. Despite their widespread adoption, concerns have emerged regarding a potential association between GLP-1 RAs and an increased risk of thyroid cancer. This study addresses a critical gap by analyzing real-world safety data to better understand this potential link, particularly comparing different GLP-1 RA compounds and the dual GLP-1/GIP agonist.
Study Design
Researchers retrieved Individual Case Safety Reports (ICSRs) from the EudraVigilance (EV) database between January 1, 2022, and September 26, 2024. The analysis focused on ICSRs where GLP-1 RAs (semaglutide, liraglutide, exenatide, lixisenatide, dulaglutide) or the dual GLP-1/GIP agonist tirzepatide were listed as suspected drugs. A disproportionality analysis was performed using the reporting odds ratio (ROR) to compare the probability of thyroid cancer-related adverse events among these compounds. A sensitivity analysis was also conducted across stratified therapeutic groups.
Results
The analysis included a total of 34,956 ICSRs, predominantly from adult and elderly female patients. The most frequently reported System Organ Classes (SOCs) were "gastrointestinal disorders," "general disorders and administration site conditions," and "injury, poisoning and procedural complications." The disproportionality analysis revealed a statistically significant finding regarding thyroid cancer-related adverse events:
Semaglutide demonstrated a lower probability of reporting thyroid cancer-related adverse events compared to tirzepatide (ROR = 0.54, 95% CI 0.37-0.81, p < 0.05). This indicates that the odds of reporting thyroid cancer-related AEs were approximately 46% lower for semaglutide than for tirzepatide in this dataset. However, the subsequent sensitivity analysis, which considered different therapeutic indications, did not identify any significant signals across the stratified groups, suggesting the observed disproportionality might be specific to the direct comparison between these two agents rather than a broader class effect across all indications.
Key Findings
- A total of 34,956 ICSRs involving GLP-1 RAs and tirzepatide were analyzed.
- The majority of adverse events were reported by adult and elderly female patients.
- Semaglutide showed a 46% lower probability of thyroid cancer-related AEs compared to tirzepatide (ROR = 0.54).
- The comparison between semaglutide and tirzepatide was statistically significant (p < 0.05).
- Sensitivity analysis across stratified therapeutic groups revealed no other significant signals.
Why It Matters
This pharmacovigilance study provides initial real-world insights into the comparative safety profiles of GLP-1 RAs and tirzepatide concerning thyroid cancer. For clinicians and patients, these data suggest a potentially differentiated risk profile among these agents, particularly between semaglutide and tirzepatide. While not establishing causality, the observed lower reporting odds for semaglutide could influence prescribing decisions, especially for patients with pre-existing thyroid concerns or risk factors. This finding underscores the importance of continued post-market surveillance and necessitates further rigorous, controlled studies to confirm any causal relationship and refine risk stratification. It highlights that even within a drug class, individual compounds may exhibit distinct safety signals that warrant careful consideration.
semaglutide
tirzepatide
glp-1-agonist
gip-agonist
thyroid-cancer
pharmacovigilance