Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
J Clin Endocrinol Metab. 2021 Jun 16;106(7):2133-2145. doi: 10.1210/clinem/dgab274.
SGLT2is are first-line antidiabetic agents with demonstrated cardiovascular benefits. Prior meta-analyses have examined adverse events (AEs) associated with these drugs in general, but such knowledge needs to be updated with the results of more recent trials. In addition, the occurrence of various AEs with different underlying diseases is unknown.
This meta-analysis aimed to investigate the occurrence of various AEs associated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) and to examine the level of risk of AEs in patients with different underlying diseases.
We conducted a quantitative meta-analysis of randomized controlled trials (RCTs) retrieved from the MEDLINE and EMBASE databases and the Cochrane library on January 31, 2021. Outcomes of interest included 4 overall safety outcomes (AEs) and 12 specified safety outcomes. Further analyses were performed on various subgroups, which were defined based on the status of diabetes mellitus (DM), atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease, and congestive heart failure, and by the dosage of SGLT2i (high dose vs low dose).
Our analysis included 10 eligible studies with a total of 71 553 participants. The meta-analysis showed that SGLT2i led to increased risks of genital infection (risk ratio [RR] 3.56, 95% CI 2.84-4.46), urinary tract infection (RR 1.06, 95% CI 1.00-1.12), diabetic ketoacidosis (RR 2.23, 95% CI 1.36-3.63), and volume depletion (RR 1.14, 95% CI 1.06-1.23). However, the use of SGLT2i was associated with reduced risks of any serious AE (RR 0.92, 95% CI 0.90-0.94), acute kidney injury (AKI) (RR 0.84, 95% CI 0.77-0.91), and hyperkalemia (RR 0.84, 95% CI 0.72-0.99). Within the different subgroups, the risk of amputation was higher in patients with ASCVD than in those without (RR 1.44 vs 0.96, P = .066).
The use of SGLT2is is generally safe. SGLT2is may be associated with increased risks of genital infection but are protective against AKI. Of note, the risk of amputation was higher in patients with ASCVD. The key to the safe use of SGLT2is lies in the identification of high-risk populations and close surveillance of patients after treatment.
SGLT2is 是具有心血管获益证据的一线抗糖尿病药物。先前的荟萃分析已经研究了这些药物的总体不良事件（AE），但需要根据最近试验的结果更新这些知识。此外，不同基础疾病的各种 AE 的发生情况尚不清楚。
本荟萃分析旨在研究钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2is）相关的各种 AE 的发生情况，并研究不同基础疾病患者发生 AE 的风险水平。
我们于 2021 年 1 月 31 日从 MEDLINE 和 EMBASE 数据库以及 Cochrane 图书馆进行了一项针对随机对照试验（RCT）的定量荟萃分析。感兴趣的结局包括 4 项总体安全性结局（AE）和 12 项特定安全性结局。进一步的分析是基于糖尿病（DM）、动脉粥样硬化性心血管疾病（ASCVD）、慢性肾脏病和充血性心力衰竭的状态以及 SGLT2i 的剂量（高剂量与低剂量）进行的。
我们的分析包括 10 项符合条件的研究，共纳入 71553 名参与者。荟萃分析显示，SGLT2i 导致生殖器感染（风险比 [RR] 3.56，95%置信区间 [CI] 2.84-4.46）、尿路感染（RR 1.06，95%CI 1.00-1.12）、糖尿病酮症酸中毒（RR 2.23，95%CI 1.36-3.63）和容量耗竭（RR 1.14，95%CI 1.06-1.23）的风险增加。然而，使用 SGLT2i 与任何严重 AE（RR 0.92，95%CI 0.90-0.94）、急性肾损伤（AKI）（RR 0.84，95%CI 0.77-0.91）和高钾血症（RR 0.84，95%CI 0.72-0.99）的风险降低相关。在不同的亚组中，ASCVD 患者的截肢风险高于无 ASCVD 患者（RR 1.44 比 0.96，P =.066）。
SGLT2is 的使用总体上是安全的。SGLT2is 可能与生殖器感染风险增加有关，但对 AKI 有保护作用。值得注意的是，ASCVD 患者的截肢风险更高。安全使用 SGLT2is 的关键在于识别高危人群，并在治疗后密切监测患者。
