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Safety of Glucagon-Like Peptide-1 Receptor Agonists: A Real-World Study Based on the US FDA Adverse Event Reporting System Database

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Abstract

Background and Objective

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used as adjunctive therapy to lifestyle intervention and metformin treatment in type 2 diabetes mellitus patients, as most GLP-1RAs have cardiovascular benefits; however, a number of adverse events (AEs) have been reported in postmarketing surveillance.

Objective

The aim of this study was to describe the AEs associated with GLP-1RA monotherapy and identify important medical event (IME) signals for GLP-1RAs.

Methods

Data from 1 April 2005 to 31 December 2021 from the US FDA Adverse Event Reporting System (FAERS) database were extracted to conduct disproportionality analysis and Bayesian analysis. AEs and IMEs were classified by system organ classes (SOCs) and preferred terms (PTs) according to the Medical Dictionary for Regulatory Activities (MedDRA®). The reporting odds ratio (ROR) and information component (IC) were used to indicate the disproportionality.

Results

A total of 71,515 records involving GLP-1RA monotherapy were submitted to the database, of which 16,350 records were GLP-1RA/IME pairs. Significant disproportionality emerged in five SOCs: ‘gastrointestinal disorders’ (n = 13,104; lower end of the 95% confidence interval (CI) of the IC [IC025] = 1.34), ‘investigations’ (n = 6889; IC025 = 0.64), ‘metabolism and nutrition disorders’ (n = 2943; IC025 = 0.44), ‘neoplasms benign/malignant’ (n = 1989; IC025 = 0.01), and ‘hepatobiliary disorders’ (n = 1497; IC025 = 0.38). The most common AEs were pancreatitis, nausea, and weight decrease. Unexpected significant AEs were detected, such as ileus, osteomyelitis, renal cell carcinoma, nephrolithiasis, and drug-induced liver injury.

Conclusion

The majority of AEs have been listed in the prescribing information or reported in previous studies, however we found significant disproportionality in some specific tumor- and liver-related AEs. Clinicians should pay more attention to the newly detected disproportionality that may be triggered by GLP-1RAs, especially in the vulnerable population after long-term use. Considering the limitations of the FAERS database, there is a need for additional pharmacoepidemiological approaches to validate the results of this study.

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Author notes

  1. Tingxi Wu and Yang Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 119 Nansihuan West Road, Fengtai District, Beijing, 100070, China

    Tingxi Wu, Kefu Yu & Zhigang Zhao

  2. Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, 95 Yongan Road, Xicheng District, Beijing, 100050, China

    Yang Zhang

  3. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China

    Yang Zhang

  4. Center of Excellence for Omics Research, National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Yanfeng Shi

  5. Department of Pharmacy, Peking University People’s Hospital, Beijing, China

    Mei Zhao

  6. School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China

    Shangyi Liu

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  1. Tingxi Wu
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Correspondence to Yang Zhang or Zhigang Zhao.

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Funding

No funding was received to conduct this study.

Author contributions

Tingxi Wu and Yang Zhang designed the research, analyzed the data, and wrote a draft of the manuscript. Yanfeng Shi, Shangyi Liu, Kefu Yu and Mei Zhao contributed to the data collection and analysis. Yang Zhang and Zhigang Zhao directed the research and revised the manuscript.

Conflicts of interest

Tingxi Wu, Yang Zhang, Yanfeng Shi, Kefu Yu, Mei Zhao, Shangyi Liu, and Zhigang Zhao have no conflicts of interest to disclose.

Availability of data and material

The data are available in the FAERS (https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html).

Ethics approval

No institutional ethics approval was required because this study utilized anonymized data from an open-access database.

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Wu, T., Zhang, Y., Shi, Y. et al. Safety of Glucagon-Like Peptide-1 Receptor Agonists: A Real-World Study Based on the US FDA Adverse Event Reporting System Database. Clin Drug Investig 42, 965–975 (2022). https://doi.org/10.1007/s40261-022-01202-1

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