Premium
Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data
Author(s) -
Blau Jenny E.,
Tella Sri Harsha,
Taylor Simeon I.,
Rother Kristina I.
Publication year - 2017
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2924
Subject(s) - medicine , diabetic ketoacidosis , empagliflozin , canagliflozin , dapagliflozin , acidosis , type 2 diabetes , adverse event reporting system , saxagliptin , population , ketoacidosis , metabolic acidosis , diabetes mellitus , adverse effect , intensive care medicine , type 1 diabetes , sitagliptin , insulin , endocrinology , environmental health
Abstract Background Regulatory agencies have concluded that sodium glucose cotransporter 2 (SGLT2) inhibitors lead to ketoacidosis, but published literature on this point remains controversial. Methods We searched the FDA Adverse Event Reporting System (FAERS) for reports of acidosis in patients treated with canagliflozin, dapagliflozin, or empagliflozin (from the date of each drug's FDA approval until May 15, 2015). We compared the number of SGLT2 inhibitor‐related reports to reports of acidosis in patients treated with the 2 most commonly used DPP4 inhibitors: sitagliptin and saxagliptin. We estimated relative risks of acidosis by relating the number of reports to cumulative drug sales (a surrogate for patient exposure). Results FAERS contained 259 reports of acidosis (including 192 reports of ketoacidosis) for SGLT2 inhibitors compared with 477 reports of acidosis for DPP4 inhibitors (including 71 reports of ketoacidosis). Based on estimated patient exposure, the overall risk of developing acidosis was ~14‐fold higher for SGLT2 inhibitors. Among 51 SGLT2 inhibitor‐related reports with quantifiable metabolic information, 20 cases occurred in patients with type 1 diabetes (T1D), 25 in type 2 diabetes (T2D), and 6 in patients with unspecified type of diabetes. After excluding patients with T1D and focusing on patients identified as having T2D, we estimate that SGLT2 inhibitors were associated with ~7‐fold increase in developing acidosis. Seventy‐one percent had euglycemic ketoacidosis. Conclusions Our results support the FDA's warning that SGLT2 inhibitors lead to ketoacidosis, as evidenced by an increased reporting rate for acidosis above that in a comparator population treated with DPP4 inhibitors.