Excavation and Evaluation of ADR Signals of SGLT 2 Inhibitors / 中国药房

ABSTRACT

OBJECTIVE：To excavate and evaluate ADR signals of SGLT 2 inhibitors as canagliflozin ，dapagliflozin and empagliflozin，and to provide reference for rational drug use in the clinic. METHODS ：The proportional reporting ratio （PRR）and reporting odds ratio （ROR）were used to find the adverse drug reactions （ADR）signal of SGLT 2 inhibitors as canagliflozin ， dapagliflozin and empagliflozin from the second quarter of 2013 to the third quarter of 2020 in the US FDA Adverse Event Reporting System （FAERS）. The basic information （including gender ，age，reporting year ，reporting country ，severe ADR ）and safety warning signals of corresponding patients in ADR report were analyzed. RESULTS ：Among 6 029 375 ADR reports ，SGLT2 inhibitors of 43 807 ADR reports were concomitant and suspected drugs ；there were 19 301 ADR reports of canagliflozin ，10 960 ADR reports of dapagliflozin ，13 546 ADR reports of empagliflozin. Except for the ADR patients with unknown gender and missing age ，the gender distribution of the included reports was balanced ，mainly in the range of 50-75 years old. The reporting year was mainly in 2018，and the main reporting country was the United States ，with“hospitalization or prolonged hospitalization ” as the main serious ADR. A total of 573 ADR signals were obtained ，involving 26 systems，mainly focusing on metabolic and nutritional diseases ，endocrine disorders ，kidney and urinary system disease ，infection and invasion diseases ，etc. The results showed that there were 14 main ADR signals in the top 10 ADR of canagliflozin ，dapagliflozin and empagliflozin. The strongest ADR signals of dapagliflozin and empagliflozin were ketoacidosis （PRR＝119.64/140.11，95％CI lower limit of ROR ＝148.28/ 178.78）and fungal infection （PRR＝47.76/34.77，95％ CI lower limit of ROR ＝50.69/36.28）；except above signals in addition ， toe amputation （PRR＝489.79，95％CI lower limit of ROR ＝520.15）and osteomyelitis （PRR＝61.42，95％CI lower limit of ROR＝65.38）were strong in the ADR signals of canagliflozin. CONCLUSIONS ：SGLT2 inhibitors have a higher security risk in metabolic and nutritional diseases ，endocrine disorders ，kidney and urinary system ，and infection and intrusion diseases. Dapagliflozin，canagliflozin and empag liflozin are prone to cause ADR such as ketoacidosis and fungal infection ，while canagliflozin is easy to cause ADRs such as toe amputation and osteomyelitis.