Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials
Sodium-glucose co-transporter-2 inhibitors and the risk of diabetic ketoacidosis in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials
复制标题
钠-葡萄糖协同转运蛋白 2 抑制剂与 2 型糖尿病患者发生糖尿病酮症酸中毒的风险：随机对照试验的系统评价和荟萃分析
DOI：
10.1111/dom.14075
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发表时间：
2020-05-21
影响因子：
5.8
通讯作者：
Sun, Xin
中科院分区：
文献类型：
--
作者：
Liu, Jiali;Li, Ling;Sun, Xin
目的评价钠葡萄糖醛酸转运蛋白2（SGLT 2）抑制剂对2型糖尿病酮症酸中毒（DKA）的影响。材料和方法我们检索PubMed、EMBASE、科克伦对照试验中心（CENTRAL）以及从开始到2019年6月13日的随机对照试验（RCT），比较SGLT 2抑制剂与对照治疗2型糖尿病患者的效果。成对的评审员独立筛选引文，评估偏倚风险并提取数据。Peto方法用作汇总SGLT 2抑制剂对DKA影响的主要方法。采用替代效应指标（风险比）或合并方法（Mantel-Haenszel）进行敏感性分析，对零事件试验或广义线性混合模型使用连续性校正0.5。进行了6项预先计划的亚组分析，以探索异质性。结果共纳入39项随机对照试验，涉及60 580例患者，85例DKA事件。与对照组相比，SGLT 2抑制剂与DKA风险增加具有统计学相关性（SGLT 2抑制剂：62/34 961 [0.18%] vs.对照：23/25 211 [0.09%]，Peto比值比[OR] 2.13，95%置信区间[CI] 1.38 - 3.27，I-2 = 8%; RD增加1.7起事件，5年内95% CI增加0.6至3.4起事件/1000;高质量证据）。敏感性分析显示了类似的结果。按平均年龄（相互作用P = 0.02）和随访时间（相互作用P = 0.03）进行的亚组分析显示，老年患者（年龄≥ 60岁）和SGLT 2抑制剂使用时间较长的患者（>52周）的相对效应较大。不同年龄或随访患者之间的治疗效果可能存在明显差异，这表明长期使用SGLT 2抑制剂的患者或老年患者应谨慎。
Aim To assess the effects of sodium-glucoseco-transporter-2 (SGLT2) inhibitors on diabetic ketoacidosis (DKA) in patients with type 2 diabetes.Materials and Methods We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and from inception to 13 June 2019 for randomized controlled trials (RCTs) that compared SGLT2 inhibitors with control in patients with type 2 diabetes. Paired reviewers independently screened citations, assessed the risk of bias and extracted data. Peto's method was used as the primary approach to pool the effect of SGLT2 inhibitors on DKA. Sensitivity analyses with the alternative effect measure (risk ratio) or pooling method (Mantel-Haenszel), the use of continuity correction of 0.5 for zero-event trials or a generalized linear mixed model were conducted. Six preplanned subgroup analyses were performed to explore heterogeneity. The grading of recommendations assessment, development and evaluation (GRADE) approach was used to rate the quality of evidence.Results A total of 39 RCTs were included, involving 60 580 patients and 85 DKA events. SGLT2 inhibitors were statistically associated with an increased risk of DKA versus control (SGLT2 inhibitors: 62/34 961 [0.18%] vs. control: 23/25 211 [0.09%], Peto odds ratio [OR] 2.13, 95% confidence interval [CI] 1.38 to 3.27, I-2 = 8%; RD 1.7 more events, 95% CI 0.6 more to 3.4 more events per 1000 over 5 years; high-quality evidence). Sensitivity analyses showed similar results. The subgroup analyses by mean age (interaction P = 0 .02) and length of follow-up (interaction P = 0 .03) showed a larger relative effect among older patients (aged >= 60 years) and those with longer use of SGLT2 inhibitors (>52 weeks).Conclusions High-quality evidence suggests that SGLT2 inhibitors may increase the risk of DKA in patients with type 2 diabetes. The apparent differences in treatment effects among patients of a different age or follow-up were probable, suggesting the advisability of caution in patients with long-term use of SGLT2 inhibitors or in older patients.