Incretin-Based Drugs for Obesity: Common and Drug-Specific Reporting Patterns of Adverse Drug Reactions—A Comparative Disproportionality Analysis Using EudraVigilance Reports Integrating SmPC Data
6 affiliations
- 1Endocrinology Department, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy, 3-5 Louis Pasteur Street, 400349 Cluj-Napoca, Romania
- 2Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy, 6A Louis Pasteur Street, 400349 Cluj-Napoca, Romania
- 3Preclinical Department, Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550169 Sibiu, Romania
- 4Internal Medicine Department, Medical Clinic No. 1, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006 Cluj-Napoca, Romania
- 5Interventional Cardiology Department, Cluj County Emergency Hospital, 400006 Cluj-Napoca, Romania
- 6Association for Excellence in Pharmaceutical Education and Research, 550169 Sibiu, Romania
Abstract
Background: With the increasing widespread use of GLP-1 RA and dual GIP/GLP-1 RAs in the treatment of obesity, their safety profile remains a concern for healthcare professionals (HPs). Objective: This study aimed to characterize and evaluate safety data from the EudraVigilance (EV) database for semaglutide (SEM), liraglutide (LIR), and tirzepatide (TIR). Methods: A hierarchical pharmacovigilance approach was applied, integrating SOC- and PT-level analyses with SmPC-based evaluation and both frequentist (ROR, 95% CI) and Bayesian (IC025) disproportionality methods. Within each molecule, reporter type–stratified analyses were performed, while across all molecules, disproportionality analyses were conducted separately in HP reports and in the full database to identify reporting patterns and potential safety signals, including those not described in the SmPCs. Results: Some ADRs, listed in the SmPC of only one or two of the three GLP1-RAs were also reported in the EV database for the other agents whose SmPCs do not specify these ADRs including optic ischemic neuropathy (TIR: 0.28% and LIR: 0.17%), alopecia (LIR: 0.81%), headache (TIR: 2.51%), intestinal obstruction (TIR: 1.55%), angioedema (LIR: 0.19%), hypersensitivity (SEM: 0.58% and LIR: 0.73%), etc. Pancreatitis, in particular, showed a significant but low-magnitude signal, being more frequently reported by HPs compared with non-HPs across all three GLP1-RAs. Additionally, statistically significant signals (IC025 > 0) were observed in both the HPs and full datasets. For example, for SEM vs. TIR, signals were identified for optic ischemic neuropathy (0.17; 0.13), gallbladder disorder (0.09; 0.11), and dysesthesia (0.42; 0.43), respectively. For TIR vs. SEM, signals were observed for injection site erythema (0.05; 0.11), injection site pruritus (0.01; 0.11), and injection site reaction (0.02; 0.08). Conclusions: These findings suggest potential safety signals beyond current SmPC information, emphasizing the need for continuous pharmacovigilance and cautious interpretation of reporting biases.
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BibTeX
@article{ilie2026incretinbased,
title = {{Incretin-Based Drugs for Obesity: Common and Drug-Specific Reporting Patterns of Adverse Drug Reactions—A Comparative Disproportionality Analysis Using EudraVigilance Reports Integrating SmPC Data}},
author = {Ioana Rada Popa Ilie and Stéliana Ghibu and Anca Butucă and Carmen Maximiliana Dobrea and Adina Frum and Călin Homorodean and Adriana Aurelia Chiş and Claudiu Morgovan},
journal = {Pharmaceuticals},
year = {2026},
month = may,
doi = {10.3390/ph19060876},
url = {https://doi.org/10.3390/ph19060876},
note = {CC BY},
}
RIS
TY - JOUR
TI - Incretin-Based Drugs for Obesity: Common and Drug-Specific Reporting Patterns of Adverse Drug Reactions—A Comparative Disproportionality Analysis Using EudraVigilance Reports Integrating SmPC Data
AU - Ioana Rada Popa Ilie
AU - Stéliana Ghibu
AU - Anca Butucă
AU - Carmen Maximiliana Dobrea
AU - Adina Frum
AU - Călin Homorodean
AU - Adriana Aurelia Chiş
AU - Claudiu Morgovan
PY - 2026
DA - 2026/05/31
JO - Pharmaceuticals
DO - 10.3390/ph19060876
UR - https://doi.org/10.3390/ph19060876
AB - Background: With the increasing widespread use of GLP-1 RA and dual GIP/GLP-1 RAs in the treatment of obesity, their safety profile remains a concern for healthcare professionals (HPs). Objective: This study aimed to characterize and evaluate safety data from the EudraVigilance (EV) database for semaglutide (SEM), liraglutide (LIR), and tirzepatide (TIR). Methods: A hierarchical pharmacovigilance approach was applied, integrating SOC- and PT-level analyses with SmPC-based evaluation and both frequentist (ROR, 95% CI) and Bayesian (IC025) disproportionality methods. Within each molecule, reporter type–stratified analyses were performed, while across all molecules, disproportionality analyses were conducted separately in HP reports and in the full database to identify reporting patterns and potential safety signals, including those not described in the SmPCs. Results: Some ADRs, listed in the SmPC of only one or two of the three GLP1-RAs were also reported in the EV database for the other agents whose SmPCs do not specify these ADRs including optic ischemic neuropathy (TIR: 0.28% and LIR: 0.17%), alopecia (LIR: 0.81%), headache (TIR: 2.51%), intestinal obstruction (TIR: 1.55%), angioedema (LIR: 0.19%), hypersensitivity (SEM: 0.58% and LIR: 0.73%), etc. Pancreatitis, in particular, showed a significant but low-magnitude signal, being more frequently reported by HPs compared with non-HPs across all three GLP1-RAs. Additionally, statistically significant signals (IC025 > 0) were observed in both the HPs and full datasets. For example, for SEM vs. TIR, signals were identified for optic ischemic neuropathy (0.17; 0.13), gallbladder disorder (0.09; 0.11), and dysesthesia (0.42; 0.43), respectively. For TIR vs. SEM, signals were observed for injection site erythema (0.05; 0.11), injection site pruritus (0.01; 0.11), and injection site reaction (0.02; 0.08). Conclusions: These findings suggest potential safety signals beyond current SmPC information, emphasizing the need for continuous pharmacovigilance and cautious interpretation of reporting biases.
SN - 1424-8247
ER -