Tirzepatide safety in EudraVigilance: descriptive and disproportionality analysis of preferred terms related to suboptimal treatment outcomes and drug-use-related issues.
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).
Retrospective pharmacovigilance study using descriptive and disproportionality analyses of reports retrieved from the EV database.
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.
Reporting ORs (RORs) with 95% CIs for selected Preferred Terms (PT) related to drug-use issues.
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.
This study complements existing evidence from clinical trials and current clinical practice.
Retrospective pharmacovigilance study using descriptive and disproportionality analyses of reports retrieved from the EV database.
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.
Reporting ORs (RORs) with 95% CIs for selected Preferred Terms (PT) related to drug-use issues.
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.
This study complements existing evidence from clinical trials and current clinical practice.
Authors
Popa Ilie Popa Ilie, Ghibu Ghibu, Butuca Butuca, Dobrea Dobrea, Frum Frum, Stoicescu Stoicescu, Homorodean Homorodean, Gligor Gligor, Morgovan Morgovan
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