Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data.
Ketoacidosis associated with SGLT2 inhibitor treatment: Analysis of FAERS data.
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DOI：
10.1002/dmrr.2924
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发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
Rother KI
中科院分区：
文献类型：
--
作者：
Blau JE;Tella SH;Taylor SI;Rother KI
监管机构已经得出结论，钠葡萄糖共转运蛋白2(SGLT2)抑制剂会导致酮症酸中毒，但已发表的关于这一点的文献仍然存在争议。我们在FDA不良事件报告系统(FAERS)中搜索使用Canagliflzin、Dapagliflzin或empagliflzin治疗的患者的酸中毒报告(从每种药物获得FDA批准之日起至2015年5月15日)。我们比较了使用两种最常用的DPP4抑制剂：西格列汀和萨格列汀治疗的患者中与SGLT2抑制剂相关的报告数量和酸中毒的报告。我们通过将报告数量与累计药物销售量(患者暴露的替代物)联系起来，估计了酸中毒的相对风险。FAERS包含259例SGLT2抑制剂酸中毒报告(包括192例酮症酸中毒报告)，而477例DPP4抑制剂酸中毒报告(包括71例酮症酸中毒报告)。根据估计的患者暴露情况，SGLT2抑制剂发生酸中毒的总体风险高出约14倍。在51篇具有可量化代谢信息的SGLT2抑制剂相关报告中，20例发生在1型糖尿病(T1D)患者，25例发生在2型糖尿病(T2D)，6例发生在未指明类型的糖尿病患者。在排除T1D患者并聚焦于被确认为T2D的患者后，我们估计SGLT2抑制剂与发展为酸中毒的~7倍相关。71%的患者患有正糖性酮症酸中毒。我们的结果支持FDA的警告，即SGLT2抑制剂会导致酮症酸中毒，酸中毒的报告率高于使用DPP4抑制剂治疗的对照人群，这是明证。
Regulatory agencies have concluded that sodiumglucose cotransporter 2 (SGLT2) inhibitors lead to ketoacidosis, but published literature on this point remains controversial. 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). 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 withT1D 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. 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.
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