Tirzepatide safety in EudraVigilance: descriptive and disproportionality analysis of preferred terms related to suboptimal treatment outcomes and drug-use-related issues
6 affiliations
- 1Department of Endocrinology, Faculty of Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania
- 2Department of Pharmacology, Physiology and Pathophysiology, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania
- 3Preclinical Department, Faculty of Medicine, Lucian Blaga University of Sibiu, Sibiu, SB, Romania
- 4Department of Cardiology, Vth Medical Clinic, Faculty of Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania
- 5Medical Clinic No. 1, Internal Medicine Department, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, CJ, Romania
- 6Interventional Cardiology Department, Cluj-Napoca County Emergency Hospital, Cluj-Napoca, CJ, Romania
Abstract
Objective: As obesity and diabetes are on the verge of an alarming growth, so is the use of tirzepatide, a novel dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) and currently the most effective weight loss-drug. This research aimed to identify reporting patterns related to suboptimal therapeutic outcomes and tirzepatide-related drug-use issues, mining the EudraVigilance (EV).
Design: Retrospective pharmacovigilance study using descriptive and disproportionality analyses of reports retrieved from the EV database.
Settings: Analysis of individual case safety reports involving tirzepatide in comparison with other GLP-1 RAs in the overall dataset (healthcare professionals (HP) and non-HP reports combined) and in the HP group.
Outcome measures: Reporting ORs (RORs) with 95% CIs for selected Preferred Terms (PT) related to drug-use issues.
Results: Among all analysed PTs, the most frequently reported were ‘Off-label use’ (n=1521), ‘Drug ineffective’ (n=425) and ‘Off-label use device’ (n=99). PTs in HP reports showed lower reporting odds compared with non-HP reports. In the overall dataset, reports involving tirzepatide showed lower reporting odds of the PT ‘Drug ineffective’ than those involving liraglutide (ROR 0.61, 95% CI 0.54 to 0.70), dulaglutide (ROR 0.72, 95% CI 0.63 to 0.82), exenatide (ROR 0.78, 95% CI 0.67 to 0.92) and semaglutide (ROR 0.81, 95% CI 0.72 to 0.91). However, in HP reports, no difference in reporting odds was observed between tirzepatide and semaglutide. A different pattern was observed for ‘off-label use’ in the full dataset, with higher reporting odds for tirzepatide vs lixisenatide, dulaglutide and liraglutide, but lower reporting odds vs semaglutide (ROR 0.52, 95% CI 0.49 to 0.55). In contrast, a higher reporting odd for the PT ‘off-label use of device’ was observed for tirzepatide versus semaglutide (ROR 43.47, 95% CI 16.00 to 118.13) in the overall reports; however, this finding should be interpreted with caution given the wide CI.
Conclusions: This study complements existing evidence from clinical trials and current clinical practice.
Related
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- Diabetic Retinal Disease Onset and Progression During Established Semaglutide or Tirzepatide Treatment: A Retrospective Comparative Cohort Study With a Descriptive Regional Nonarteritic Anterior Ischemic Optic Neuropathy (NAION) Review.
- Safety of nirsevimab in children aged 0-24 months: Analysis based on EudraVigilance data (2023-2025).
BibTeX
@article{ilie2026tirzepatide,
title = {{Tirzepatide safety in EudraVigilance: descriptive and disproportionality analysis of preferred terms related to suboptimal treatment outcomes and drug-use-related issues}},
author = {Ioana Rada Popa Ilie and Steliana Ghibu and Anca Butuca and Carmen Maximiliana Dobrea and Adina Frum and Laurentiu Stoicescu and Cãlin Homorodean and Felicia Gabriela Gligor and Claudiu Morgovan},
journal = {BMJ Open},
year = {2026},
month = oct,
doi = {10.1136/bmjopen-2026-120507},
url = {https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2026-120507},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Tirzepatide safety in EudraVigilance: descriptive and disproportionality analysis of preferred terms related to suboptimal treatment outcomes and drug-use-related issues
AU - Ioana Rada Popa Ilie
AU - Steliana Ghibu
AU - Anca Butuca
AU - Carmen Maximiliana Dobrea
AU - Adina Frum
AU - Laurentiu Stoicescu
AU - Cãlin Homorodean
AU - Felicia Gabriela Gligor
AU - Claudiu Morgovan
PY - 2026
DA - 2026/10/01
JO - BMJ Open
DO - 10.1136/bmjopen-2026-120507
UR - https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2026-120507
AB - Objective: As obesity and diabetes are on the verge of an alarming growth, so is the use of tirzepatide, a novel dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) and currently the most effective weight loss-drug. This research aimed to identify reporting patterns related to suboptimal therapeutic outcomes and tirzepatide-related drug-use issues, mining the EudraVigilance (EV). Design: Retrospective pharmacovigilance study using descriptive and disproportionality analyses of reports retrieved from the EV database. Settings: Analysis of individual case safety reports involving tirzepatide in comparison with other GLP-1 RAs in the overall dataset (healthcare professionals (HP) and non-HP reports combined) and in the HP group. Outcome measures: Reporting ORs (RORs) with 95% CIs for selected Preferred Terms (PT) related to drug-use issues. Results: Among all analysed PTs, the most frequently reported were ‘Off-label use’ (n=1521), ‘Drug ineffective’ (n=425) and ‘Off-label use device’ (n=99). PTs in HP reports showed lower reporting odds compared with non-HP reports. In the overall dataset, reports involving tirzepatide showed lower reporting odds of the PT ‘Drug ineffective’ than those involving liraglutide (ROR 0.61, 95% CI 0.54 to 0.70), dulaglutide (ROR 0.72, 95% CI 0.63 to 0.82), exenatide (ROR 0.78, 95% CI 0.67 to 0.92) and semaglutide (ROR 0.81, 95% CI 0.72 to 0.91). However, in HP reports, no difference in reporting odds was observed between tirzepatide and semaglutide. A different pattern was observed for ‘off-label use’ in the full dataset, with higher reporting odds for tirzepatide vs lixisenatide, dulaglutide and liraglutide, but lower reporting odds vs semaglutide (ROR 0.52, 95% CI 0.49 to 0.55). In contrast, a higher reporting odd for the PT ‘off-label use of device’ was observed for tirzepatide versus semaglutide (ROR 43.47, 95% CI 16.00 to 118.13) in the overall reports; however, this finding should be interpreted with caution given the wide CI. Conclusions: This study complements existing evidence from clinical trials and current clinical practice.
SN - 2044-6055
SN - 2044-6055
ER -