目的 基于美国食品药品管理局不良事件报告系统（FAERS）数据库和日本药物不良事件报告（JADER）数据库，挖掘与分析已上市的二肽基肽酶-Ⅳ（DPP-4）抑制剂（西格列汀、维格列汀、沙格列汀、阿格列汀、利格列汀、替格列汀、曲格列汀、奥格列汀）骨折相关不良反应信号，为2型糖尿病伴有骨疾病患者的安全合理用药提供参考。方法 收集FAERS数据库和JADER数据库中DPP-4抑制剂与骨折相关不良事件，分别检索各类DPP-4抑制剂上市时间至2025年1月，分析性别、年龄和体质量因素对骨折相关不良事件的影响，采用报告比值比（ROR）法进行骨折相关不良事件检测，提取报告数a≥3且95%置信区间（CI）下限＞1的信号。利用国际医学用语词典（MedDRA）的首选系统器官分类（SOC）和首选术语（PT）对挖掘的信号进行统计分类和分析。结果 本研究共提取到DPP-4抑制剂骨折相关不良事件报告数为1 643例，其中包括西格列汀969例、维格列汀177例、沙格列汀120例、阿格列汀73例、利格列汀304例、替格列汀9例、曲格列汀12例、奥格列汀3例。按照MedDRA共提取出20个与骨折相关的可疑信号。不良事件报告患者年龄主要集中在＞50岁，病例上报的国家主要来自美国、日本，性别上无显著性差异，体质量≥70 kg的患者居多。本研究在对致患者不同部位骨折事件报告的分析结果显示，DPP-4抑制剂中西格列汀和沙格列汀与骨折事件的发生均无显著的相关性，而维格列汀、阿格列汀、利格列汀、替格列汀和奥格列汀与骨折风险可能有较低的相关性。结论 2型糖尿病患者应用DPP-4抑制剂时出现骨折风险较低。

Objective To excavation and analyze fracture-related adverse reaction signals of marketed dipeptidyl peptidase-Ⅳ(DPP-4) inhibitors (sitagliptin, vigagliptin, saxagliptin, alogliptin, ligagliptin, teneligliptin, trelagliptin and omarigliptin) based on the FAERS database and JADER database. To provide reference for safe and rational drug use in type 2 diabetes patients with bone disease. Methods DPP-4 inhibitors and fracture-related adverse reaction were collected from the FAERS database and the JADER database. The time of listing of each DPP-4 inhibitor to January 2025 was searched, and the effects of gender, age and weight on fracture-related adverse event were analyzed. The ROR method was used to detect fracture-related adverse event. Extract signals with report number a ≥ 3 and lower limit of 95% CI > 1. The excavation signals were statistically classified and analyzed using SOC and PT of the MedDRA. Results A total of 1 643 of adverse event related to fractures with DPP-4 inhibitor were extracted, including 969 of sitagliptin, 177 of vigliptin, 120 of saxagliptin, 73 of alogliptin, 304 of lishagliptin, 9 of teneligliptin, 12 of trelagliptin, 3 of omarigliptin. According to MedDRA, a total of 20 suspicious signals related to fractures were extracted. The age of adverse event patients was mainly > 50 years old, and the countries reported cases were mainly from the United States and Japan. There was no significant difference in gender, and most patients with body weight ≥70 kg were reported. Analysis of fracture event reports at different sites in patients showed that the DPP-4 inhibitors of midogliptin and saxagliptin were not significantly associated with the occurrence of fracture events, while vigogliptin, alogliptin and rigliptin may have a lower risk of fracture. Conclusion There is little to no increased risk of fractures when DPP-4 inhibitors are used in patients with type 2 diabetes mellitus.

R977

国家自然科学基金青年项目（82000842）；广东省医学科研基金项目（A2024138，B2025580）；广东省医院药学研究基金（2025A01002）