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. 2024 Nov;47(11):2671-2678.
doi: 10.1007/s40618-024-02441-z. Epub 2024 Aug 14.

The real-world safety profile of tirzepatide: pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database

I Caruso  1 , L Di Gioia  1 , S Di Molfetta  1 , M Caporusso  1 , A Cignarelli  1 , G P Sorice  1 , L Laviola  1 , F Giorgino  2
Affiliations

The real-world safety profile of tirzepatide: pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database

I Caruso et al. J Endocrinol Invest. 2024 Nov.

Abstract

Purpose: Randomized controlled trials with tirzepatide (TZP) displayed unprecedented glucose and body weight lowering efficacy in individuals with type 2 diabetes and/or obesity and a safety profile similar to that of glucagon-like peptide-1 receptor agonists (GLP-1RA), mainly characterized by gastrointestinal (GI) adverse events (AE). Concerns on diabetic retinopathy, pancreato-biliary disorders, and medullary thyroid cancer were also addressed. We aimed to investigate whether the same safety issues emerged from the FDA Adverse Event Reporting System (FAERS) post-marketing surveillance database.

Methods: OpenVigil 2.1-MedDRA-v24 and AERSMine (data 2004Q1-2023Q3) were used to query the FAERS database. Reports of GI AE, diabetic retinopathy, pancreato-biliary disorders, and medullary thyroid cancer were investigated. The analysis was then filtered for age, gender, and designation as primary suspect. AE occurrence with TZP was compared to insulin, sodium-glucose cotransporter-2 inhibitors, metformin, and GLP-1RA.

Results: Disproportionate reporting of GI [i.e., nausea (ROR 4.01, 95% CI 3.85-4.19)] and pancreato-biliary disorders [i.e., pancreatitis (ROR 3.63, 95% CI 3.15-4.19)], diabetic retinopathy (ROR 4.14, 95% CI 2.34-7.30), and medullary thyroid cancer (ROR 13.67, 95% CI 4.35-42.96) was detected. TZP exhibited a similar risk of GI AE and medullary thyroid cancer and a lower risk of most pancreato-biliary AE and diabetic retinopathy vs. GLP-1RA.

Conclusions: TZP was associated with an increased risk of specific AE. However, its safety profile was similar to that of GLP-1RA, without increased risk of pancreato-biliary AE, diabetic retinopathy, and medullary thyroid cancer.

Keywords: Adverse events; GIP; Tirzepatide; Type 2 diabetes.

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Conflict of interest statement

AC: AstraZeneca, Eli Lilly, Novo Nordisk, Roche Diagnostics, Sanofi Aventis. FG: AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Lifescan, Medimmune, Merck Sharp & Dohme, Medtronic, Novo Nordisk, Roche Diabetes Care, Sanofi Aventis. GPS: Amgen, Amryt, Eli Lilly, Farmitalia, Novo Nordisk, Sanofi; IC: Eli Lilly, Novo Nordisk; LDG: Eli Lilly, Lusofarmaco, Medtronic, MOVI SpA, Novo Nordisk, Roche Diabetes Care, Sanofi Aventis. LL: Abbott, AstraZeneca, Boehringer-Ingelheim, Eli Lilly, Merck Sharp & Dohme, Medtronic, Menarini, MOVI SpA, Mundipharma, Novo Nordisk, Roche Diabetes Care, Sanofi Aventis, Terumo. MC: AstraZeneca, Eli Lilly, Guidotti, Novo Nordisk; SDM: Ascensia Diabetes Care, Eli Lilly, MOVI SpA, Roche Diabetes Care.

Figures

Fig. 1
Fig. 1
Disproportionately reported adverse events (AE) of interest for tirzepatide vs. all other drugs in the FAERS database. The forest plot shows reporting odds ratios (ROR) with 95% confidence intervals for gastrointestinal, pancreato-biliary, eye-related, and thyroid-related AE for tirzepatide vs. control drugs
Fig. 2
Fig. 2
Reporting odds ratio (ROR) of adverse events (AE) of interest for tirzepatide vs. all other drugs in females vs. males. The forest plot shows ROR with 95% confidence intervals for gastrointestinal, pancreato-biliary, eye-related, and thyroid-related AE for tirzepatide vs. control drugs in females vs. males. A ROR < 1.0 indicates a disproportional lower rate of AE among reports for females
Fig. 3
Fig. 3
Reporting odds ratio of adverse events (AE) of interest for tirzepatide vs. all other drugs in individuals aged > 65 vs. 18–65 years. The forest plot shows reporting odds ratios (ROR) with 95% confidence intervals for gastrointestinal, pancreato-biliary, eye-related, and thyroid-related AE for tirzepatide vs. control drugs in individuals aged > 65 years (old) vs. individuals aged 18–65 years (young). A ROR < 1.0 indicates a disproportional lower rate of AE among reports for individuals aged > 65 years
Fig. 4
Fig. 4
Reporting odds ratio (ROR) of adverse events (AE) of interest for tirzepatide vs. all glucagon-like peptide-1 receptor agonists (GLP-1RA, A), semaglutide (B), insulin (C), sodium-glucose cotransporter-2 inhibitors (SGLT-2i, D). The forest plot shows ROR with 95% confidence intervals for gastrointestinal, pancreato-biliary, eye-related, and thyroid-related AE for tirzepatide vs. all GLP-1RA (A), semaglutide (B), insulin (C), and SGLT-2i (D). A ROR < 1.0 indicates a disproportional lower rate of AE among reports for tirzepatide
See this image and copyright information in PMC

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