Risks of amputation and fracture due to sodium glucose co-transporter 2 inhibitors: a study based on the related data in the US Food and Drug Administration Adverse Event Reporting System
10.3760/cma.j.issn.1008-5734.2019.02.007
- VernacularTitle:钠-葡萄糖共转运蛋白2抑制剂致截肢与骨折的风险:基于美国FDA不良事件报告系统相关数据的研究
- Author:
Zhenwei FANG
1
;
Jia SHI
1
;
Yang LIN
1
Author Information
1. 首都医科大学附属北京安贞医院药事部 100029
- Publication Type:Journal Article
- Keywords:
Sodium-glucose transporter 2 inhibitors;
Diabetes mellitus;
Odds ratio;
Amputation;
Fractures,bone;
Adverse drug reaction reporting systems
- From:
Adverse Drug Reactions Journal
2019;21(2):108-117
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the risks of amputation and fracture induced by sodium glucose co-transporter 2 (SGLT2) inhibitors (canagliflozin,dapagliflozin,empagliflozin,and ertugliflozin).Methods Reports of amputation and fracture events induced by SGLT2 inhibitors and non-SGLT2 inhibitors received from January 1,2004 to June 30,2018 in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database were collected.The relationship between the drugs mentioned above and the amputation and fracture events in all patients and especially in patients with diabetes mellitus,respectively,were analyzed by the method of reporting odds ratio (ROR).Results A total of 1 633 reports of SGLT2 inhibitors-induced amputation (27.66％ of 5 904 amputation event reports in the database during the study period) and 244 reports of SGLT2 inhibitors-induced fracture (0.21％ of 114 051 fracture event reports in the database during the study period) were retrieved from the database.These reports were related to canagliflozin,dapagliflozin,and empagliflozin,but not to ertugliflozin.And a total of 4 271 nonSGLT2 inhibitors-induced amputation event reports and 113 807 fracture event reports were retrieved from the database.Of the 1 633 reports of SGLT2 inhibitor-induced amputation,1 432 reports (87.69％) involved lower-limbs (led,foot,and toe) amputation,which had the highest proportion.The ROR values of all amputation events induced by overall SGLT2 inhibitors,canagliflozin,dapagliflozin,and empagliflozin in all patients were 92.70 (95％ CI:87.47-98.24),150.72 (95％ CI:141.98-160.00),6.84 (95％ CI:4.54-10.31),and 16.54 (95％ CI:12.98-21.07),respectively,and in patients with diabetes mellitus were 30.53 (95％ CI:27.81-33.51),49.68 (95％CI:45.19-54.62),2.73 (95％ CI:1.75-4.27),and 5.09 (95％ CI:3.80-6.83),respectively.The ROR values of lower-limb amputation events induced by overall SGLT2 inhibitors,canagliflozin,dapagliflozin,and empagliflozin in all patients were 103.49 (95％ CI:97.19-110.20),167.29 (95％ CI:156.82-178.45),8.38 (95％ CI:5.50-12.75),and 18.63 (95％CI:14.39-24.12),respectively,and in patients with diabetes mellitus were 30.92 (95％ CI:28.00-34.13),49.96 (95％ CI:45.18-55.24),2.95 (95％ CI:1.87-4.66) and 5.42 (95 ％ CI:4.00-7.34),respectively.The ROR values of fracture events induced by overall SGLT2 inhibitors were 0.49 (95％ CI:0.43-0.56) and 0.57 (95％ CI:0.49-0.67) in all patients and in patients with diabetes mellitus,respectively.Conclusions SGLT2 inhibitors could increase the risk of amputation in patients,especially the lower-limb amputation.The reports of amputation induced by canagliflozin had higher proportion than those induced by dapagliflozin or empagliflozin.No significant relationship between SGLT2 inhibitors and fracture was found.
