Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis A Multicenter Cohort Study
Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Diabetic Ketoacidosis A Multicenter Cohort Study
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DOI：
10.7326/m20-0289
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发表时间：
2020-09-15
影响因子：
39.2
通讯作者：
Filion, Kristian B.
中科院分区：
文献类型：
--
作者：
Douros, Antonios;Lix, Lisa M.;Filion, Kristian B.
背景资料：钠-葡萄糖协同转运蛋白-2（SGLT-2）抑制剂可增加糖尿病酮症酸中毒（DKA）的风险。目的：评估SGLT-2抑制剂与二肽基肽酶-4（DPP-4）抑制剂相比，是否与2型糖尿病患者DKA风险增加相关。设计：基于人群的队列研究; 2013年至2018年的流行新用户设计。（临床试验政府网站：NCT 04017221）设置：来自加拿大7个省和英国的电子医疗保健数据库。患者：通过使用时间条件性倾向评分将208 757名SGLT-2抑制剂新使用者与208 757名DPP-4抑制剂接受者进行匹配。测量：考克斯比例风险模型估计了比较SGLT-2抑制剂与DPP-4抑制剂治疗的DKA的研究中心特异性风险比（HR）和95% CI，通过使用随机效应模型将其合并。二次分析按分子、年龄、性别和既往接受insulin.Results分层：总体而言，在370454人年随访期间，521例患者被诊断为DKA（发病率每1000人年，1.40 [95%CI，1.29至1.53]）。与DPP-4抑制剂相比，SGLT-2抑制剂与DKA风险增加相关（发生率分别为2.03 [CI，1.83 - 2.25] vs 0.75 [CI，0.63 - 0.89]; HR，2.85 [CI，1.99 - 4.08]）。达格列净、恩格列净和卡格列净的分子特异性HR分别为1.86（CI，1.11 - 3.10）、2.52（CI，1.23 - 5.14）和3.58（CI，2.13 - 6.03）。年龄和性别并没有改变这种关联;既往接受胰岛素治疗似乎可以降低风险。局限性：存在未测量的混杂因素，大多数患者没有实验室数据，在有限数量的研究中心进行了分子特异性分析。结论：SGLT-2抑制剂与DKA风险增加近3倍相关，分子特异性分析表明存在类效应。
Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors could increase the risk for diabetic ketoacidosis (DKA).Objective: To assess whether SGLT-2 inhibitors, compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, are associated with an increased risk for DKA in patients with type 2 diabetes.Design: Population-based cohort study; prevalent new-user design between 2013 and 2018. (ClinicalTrials.gov: NCT04017221)Setting: Electronic health care databases from 7 Canadian provinces and the United Kingdom.Patients: 208 757 new users of SGLT-2 inhibitors were matched by using time-conditional propensity scores to 208 757 recipients of DPP-4 inhibitors.Measurements: Cox proportional hazards models estimated site-specific hazard ratios (HRs) with 95% CIs of DKA comparing receipt of SGLT-2 inhibitors with receipt of DPP-4 inhibitors, which were pooled by using random-effects models. Secondary analyses were stratified by molecule, age, sex, and prior receipt of insulin.Results: Overall, 521 patients were diagnosed with DKA during 370 454 person-years of follow-up (incidence rate per 1000 person-years, 1.40 [95% CI, 1.29 to 1.53]). Compared with DPP-4 inhibitors, SGLT-2 inhibitors were associated with an increased risk for DKA (incidence rate, 2.03 [CI, 1.83 to 2.25] versus 0.75 [CI, 0.63 to 0.89], respectively; HR, 2.85 [CI, 1.99 to 4.08]). Molecule-specific HRs were 1.86 (CI, 1.11 to 3.10) for dapagliflozin, 2.52 (CI, 1.23 to 5.14) for empagliflozin, and 3.58 (CI, 2.13 to 6.03) for canagliflozin. Age and sex did not modify the association; prior receipt of insulin appeared to decrease the risk.Limitations: There was unmeasured confounding and no laboratory data were available for the majority of patients, and molecule-specific analyses were conducted at a limited number of sites.Conclusion: SGLT-2 inhibitors were associated with an almost 3-fold increased risk for DKA, with molecule-specific analyses suggesting a class effect.