Xiao Yao, Zhou Min, Xiao Wenfeng
Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China.
Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, 410008, Hunan, China.
Acta Diabetol. 2024 Nov 18. doi: 10.1007/s00592-024-02415-w.
Diabetes patients are at a higher risk of fractures, and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been suggested to positively impact on bone metabolism. We aim to provide a comprehensive assessment of fracture events associated with GLP-1RAs based on pharmacovigilance data.
In this study, fracture-related adverse events (AEs) associated with GLP-1RAs and other commonly used glucose-lowering drugs were identified from Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2022). The reporting odds ratio (ROR) and adjusted ROR (adj. ROR) were used to compare the reporting of fracture-related AEs associated with insulin, GLP-1RAs, and Non GLP-1RAs, in patients with diabetes through two scenarios. This involved separately comparing each glucose-lowering drug to all other medications used in diabetic patients and reiterating after excluding insulin cases.
A total of 490,107 AE reports for patients with diabetes were identified and 98, 625 of them were for GLP-1RAs. Among all diabetes drugs, GLP-1RAs had the lowest reporting of any fracture-related AEs [adj. ROR = 0.44 (0.40-0.47)], consistent across osteoporotic fracture [adj. ROR = 0.39 (0.34-0.45)] and hip fracture [adj. ROR = 0.34 (0.28-0.41)]. Among GLP-1RA agents, albiglutide was associated with the lowest adj. ROR [0.11 (0.05-0.21)] for any fracture-related AEs. After excluded all insulin reports, GLP-1RAs retained a significantly lower adj. ROR towards any fracture [adj. ROR = 0.45 (0.40-0.50)], osteoporotic fracture [adj. ROR = 0.44 (0.37-0.52)], and hip fracture [adj. ROR = 0.43 (0.33-0.54)].
In a real-world pharmacovigilance setting, GLP-1RAs were associated with lower reporting of fracture-related AEs, indicating the protective effect of GLP-1RAs against fractures.
糖尿病患者骨折风险更高，有人提出胰高血糖素样肽-1受体激动剂（GLP-1RAs）对骨代谢有积极影响。我们旨在基于药物警戒数据对与GLP-1RAs相关的骨折事件进行全面评估。
在本研究中，从美国食品药品监督管理局不良事件报告系统（FAERS）数据库（2004 - 2022年）中识别出与GLP-1RAs及其他常用降糖药物相关的骨折相关不良事件（AEs）。报告比值比（ROR）和调整后的ROR（adj. ROR）用于通过两种情况比较糖尿病患者中与胰岛素、GLP-1RAs和非GLP-1RAs相关的骨折相关AEs的报告情况。这包括分别将每种降糖药物与糖尿病患者使用的所有其他药物进行比较，并在排除胰岛素病例后重复进行。
共识别出490,107份糖尿病患者的AE报告，其中98,625份是关于GLP-1RAs的。在所有糖尿病药物中，GLP-1RAs的任何骨折相关AEs报告率最低[adj. ROR = 0.44（0.40 - 0.47）]，在骨质疏松性骨折[adj. ROR = 0.39（0.34 - 0.45）]和髋部骨折[adj. ROR = 0.34（0.28 - 0.41）]中均一致。在GLP-1RA药物中，阿必鲁肽与任何骨折相关AEs的最低adj. ROR[0.11（0.05 - 0.21）]相关。排除所有胰岛素报告后，GLP-1RAs对任何骨折[adj. ROR = 0.45（0.40 - 0.50）]、骨质疏松性骨折[adj. ROR = 0.44（0.37 - 0.52）]和髋部骨折[adj. ROR = 0.43（0.33 - 0.54）]的adj. ROR仍显著较低。
在真实世界的药物警戒环境中，GLP-1RAs与骨折相关AEs的报告率较低相关，表明GLP-1RAs对骨折有保护作用。
