Department of General Medicine, Shenzhen Longhua District Central Hospital, Shenzhen.
Department of Endocrinology, First Affiliated Hospital of Yangtze University, Jingzhou, China.
Medicine (Baltimore). 2021 Mar 12;100(10):e25121. doi: 10.1097/MD.0000000000025121.
It is unclear whether there are false positive or negative results in the effects of sodium-glucose transporter 2 (SGLT2) inhibitors on various cardiovascular and renal outcomes in patients with type 2 diabetes. We aimed to explore this issue by a meta-analysis with trial sequential analysis.
We included randomized trials evaluating the effects of SGLT2 inhibitors on cardiorenal endpoints in type 2 diabetic patients. Eight endpoints evaluated in the study were fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, major adverse cardiovascular events (MACE), cardiovascular death or hospitalization for heart failure (CVD or HHF), all-cause death (ACD), cardiovascular death (CVD), hospitalization for heart failure (HHF), and kidney function progression (KFP). Meta-analysis and trial sequential analysis was conducted for each endpoint.
Seven randomized trials of SGLT2 inhibitors were included for pooled analysis. Compared with placebo, SGLT2 inhibitors significantly reduced the risk of MACE (HR 0.89, 95% confidence interval [CI] 0.84-0.94), MI (HR 0.91, 95% CI 0.84-0.99), CVD (HR 0.86, 95% CI 0.79-0.93), CVD or HHF (HR 0.77, 95% CI 0.73-0.82), HHF (HR 0.67, 95% CI 0.62-0.74), KFP (HR 0.63, 95% CI 0.56-0.70), and ACD (HR 0.88, 95% CI 0.83-0.94), whereas SGLT2 inhibitors did not have significant effects on stroke (HR 0.98, 95% CI 0.88-1.09). Trial sequential analyses for MI and stroke showed that cumulative Z curve did not cross trial sequential monitoring boundary and required information size, whereas those for the other 6 endpoints showed that cumulative Z curve crossed trial sequential monitoring boundary and/or required information size.
Compared with placebo, SGLT2 inhibitors conclusively reduce the risk of MACE, CVD or HHF, ACD, CVD, HHF, and KFP in patients with type 2 diabetes, whereas the effects of SGLT2 inhibitors on MI and stroke are not conclusive and need to be further assessed in future studies with the adequate sample size to reject or accept the effect size.
目前尚不清楚钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂对 2 型糖尿病患者各种心血管和肾脏结局的影响是否存在假阳性或假阴性结果。我们旨在通过具有试验序贯分析的荟萃分析来探讨这个问题。
我们纳入了评估 SGLT2 抑制剂对 2 型糖尿病患者心肾结局影响的随机试验。本研究评估了 8 个终点，分别为致死性或非致死性心肌梗死（MI）、致死性或非致死性卒、主要不良心血管事件（MACE）、心血管死亡或心力衰竭住院（CVD 或 HHF）、全因死亡（ACD）、心血管死亡（CVD）、心力衰竭住院（HHF）和肾功能进展（KFP）。对每个终点进行荟萃分析和试验序贯分析。
共纳入了 7 项 SGLT2 抑制剂的随机试验进行汇总分析。与安慰剂相比，SGLT2 抑制剂显著降低了 MACE（HR 0.89，95%置信区间 [CI] 0.84-0.94）、MI（HR 0.91，95% CI 0.84-0.99）、CVD（HR 0.86，95% CI 0.79-0.93）、CVD 或 HHF（HR 0.77，95% CI 0.73-0.82）、HHF（HR 0.67，95% CI 0.62-0.74）、KFP（HR 0.63，95% CI 0.56-0.70）和 ACD（HR 0.88，95% CI 0.83-0.94）的风险，但 SGLT2 抑制剂对卒中（HR 0.98，95% CI 0.88-1.09）没有显著影响。对 MI 和卒中等事件的试验序贯分析表明，累积 Z 曲线未穿过试验序贯监测边界和所需信息量，而对其他 6 个终点的分析表明，累积 Z 曲线穿过了试验序贯监测边界和/或需要信息量。
与安慰剂相比，SGLT2 抑制剂可显著降低 2 型糖尿病患者的 MACE、CVD 或 HHF、ACD、CVD、HHF 和 KFP 的风险，而 SGLT2 抑制剂对 MI 和卒中等事件的影响尚无定论，需要在未来的研究中进一步评估，以获得足够的样本量来拒绝或接受效应大小。
