Evaluation of the safety profile of glucagon-like peptide-1 receptor agonists: a focus on thyroid cancer-related adverse events by using the European pharmacovigilance database.
Antonietta Anatriello, Valerio Liguori, Ciro Pentella, Alessia Zinzi, Miriam Longo, Paola Caruso, Maria Ida Maiorino, Katherine Esposito, Annalisa Capuano
{"title":"Evaluation of the safety profile of glucagon-like peptide-1 receptor agonists: a focus on thyroid cancer-related adverse events by using the European pharmacovigilance database.","authors":"Antonietta Anatriello, Valerio Liguori, Ciro Pentella, Alessia Zinzi, Miriam Longo, Paola Caruso, Maria Ida Maiorino, Katherine Esposito, Annalisa Capuano","doi":"10.1007/s43440-026-00864-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The therapeutic landscape for the treatment of type 2 diabetes mellitus (T2DM) has greatly evolved with the introduction of glucagon-like peptide-1 receptor agonists (GLP-1 RAs); however, concerns regarding their potential association with thyroid cancer have emerged. The aim of this study is to analyze individual case safety reports (ICSRs) involving GLP-1 RAs, focusing on thyroid cancer-related adverse events (AEs) using the European pharmacovigilance database.</p><p><strong>Methods: </strong>ICSRs reporting GLP-1 RAs (semaglutide, liraglutide, exenatide, lixisenatide, dulaglutide) or the dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide as suspected drugs were retrieved from the EudraVigilance (EV) database from 1st January 2022 to 26th September 2024. A disproportionality analysis was performed to compare the probability of reporting thyroid cancer-related AEs among these drugs using the reporting odds ratio (ROR) and its 95% confidence interval (95% CI). Considering the different therapeutic indications, a sensitivity analysis was also conducted.</p><p><strong>Results: </strong>A total of 34,956 ICSRs were included in the analysis. The majority of AEs were experienced by adult and elderly female patients. The most reported system organ classes (SOCs) were: \"gastrointestinal disorders\", \"general disorders and administration site conditions\", and \"injury, poisoning and procedural complications\". Disproportionality analysis revealed that semaglutide had a lower probability of reporting thyroid cancer-related AEs than tirzepatide (ROR = 0.54, 95% CI 0.37-0.81, p < 0.05), whereas sensitivity analysis revealed no significant signals across stratified therapeutic groups.</p><p><strong>Conclusion: </strong>These findings should be interpreted with caution, given the inherent limitations of pharmacovigilance databases. Further studies are recommended to better assess the potential causal relationship between GLP-1 RAs and thyroid cancer.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5000,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacological Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s43440-026-00864-4","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: The therapeutic landscape for the treatment of type 2 diabetes mellitus (T2DM) has greatly evolved with the introduction of glucagon-like peptide-1 receptor agonists (GLP-1 RAs); however, concerns regarding their potential association with thyroid cancer have emerged. The aim of this study is to analyze individual case safety reports (ICSRs) involving GLP-1 RAs, focusing on thyroid cancer-related adverse events (AEs) using the European pharmacovigilance database.
Methods: ICSRs reporting GLP-1 RAs (semaglutide, liraglutide, exenatide, lixisenatide, dulaglutide) or the dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide as suspected drugs were retrieved from the EudraVigilance (EV) database from 1st January 2022 to 26th September 2024. A disproportionality analysis was performed to compare the probability of reporting thyroid cancer-related AEs among these drugs using the reporting odds ratio (ROR) and its 95% confidence interval (95% CI). Considering the different therapeutic indications, a sensitivity analysis was also conducted.
Results: A total of 34,956 ICSRs were included in the analysis. The majority of AEs were experienced by adult and elderly female patients. The most reported system organ classes (SOCs) were: "gastrointestinal disorders", "general disorders and administration site conditions", and "injury, poisoning and procedural complications". Disproportionality analysis revealed that semaglutide had a lower probability of reporting thyroid cancer-related AEs than tirzepatide (ROR = 0.54, 95% CI 0.37-0.81, p < 0.05), whereas sensitivity analysis revealed no significant signals across stratified therapeutic groups.
Conclusion: These findings should be interpreted with caution, given the inherent limitations of pharmacovigilance databases. Further studies are recommended to better assess the potential causal relationship between GLP-1 RAs and thyroid cancer.
期刊介绍：
Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures.
Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology.
Studies of plant extracts are not suitable for Pharmacological Reports.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
