The efficacy and safety of novel classes of glucose-lowering drugs for cardiovascular outcomes: a network meta-analysis of randomised clinical trials
The efficacy and safety of novel classes of glucose-lowering drugs for cardiovascular outcomes: a network meta-analysis of randomised clinical trials
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DOI：
10.1007/s00125-021-05529-w
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发表时间：
2021-09-18
期刊：
影响因子：
8.2
通讯作者：
Chen, Wen-Jone
中科院分区：
文献类型：
--
作者：
Lin, Donna Shu-Han;Lee, Jen-Kuang;Chen, Wen-Jone
目的/假设最近发布了几项关于钠-葡萄糖协同转运蛋白2抑制剂（SGLT 2 i）的心血管结局试验，包括招募充血性心力衰竭（CHF）和慢性肾病（CKD）患者的试验。因此，SGLT 2 i、胰高血糖素样肽-1受体激动剂（GLP-1 RA）和二肽基肽酶-4抑制剂（DPP-4 i）的疗效和安全性比较需要更新。患者亚组的评估，即，方法我们检索了PubMed、Embase和科克伦数据库中截至2020年12月5日发表的相关研究。比较SGLT 2 i、GLP-1 RA和DPP-4 i与安慰剂（或其他对照）或彼此之间心血管（CV）或肾脏结局的RCT符合入选条件。主要疗效终点为3点主要心血管不良事件（3 P-MACE），定义为CV死亡、非致死性心肌梗死和非致死性缺血性卒中。还分析了全因死亡率、因心力衰竭（HHF）住院和复合肾脏结局。结果本研究共纳入21项临床试验，170，930例受试者。与安慰剂相比，GLP-1 RA和SGLT 2 i的3 P-MACE风险均较低（分别为RR 0.89，95% CI 0.84，0.94和RR 0.88，95% CI 0.83，0.94）。GLP-1 RA和SGLT 2 i的3 P-MACE风险也低于DPP-4 i（分别为RR 0.89，95% CI 0.82，0.98和RR 0.89，95% CI 0.81，0.97）。SGLT 2 i与GLP-1 RA之间的比较表明，其3 P-MACE风险无差异（RR 0.99，95% CI 0.91，1.08）。与安慰剂相比，仅GLP-1 RA与卒中风险降低相关（RR 0.85，95% CI 0.76，0.94）。SGLT 2 i在降低HHF（RR 0.76，95% CI 0.68，0.84）和肾脏结局（RR 0.78，95% CI 0.65）方面优于GLP-1 RA（上级）。0.93）。亚组分析表明，SGLT 2 i和GLP-1 RA的获益在老年患者、白色和亚洲患者、确诊ASCVD患者和糖尿病持续时间较长且血糖控制较差的患者中更为明显。结论/解释SGLT 2 i和GLP-1 RA在CV和肾脏结局方面上级优于DPP-4 i。GLP-1 RA是唯一一种降低中风风险的药物。SGLT 2 i在降低HHF和肾脏结局方面具有上级优势。因此，SGLT 2 i和GLP-1 RA之间的选择应根据患者特征进行个体化。
Aims/hypothesis Several cardiovascular outcome trials on sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been released recently, including trials enrolling patients with congestive heart failure (CHF) and chronic kidney disease (CKD). Comparisons of the efficacy and safety of SGLT2i, glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) thus require an update. Assessments in patient subgroups, i.e., as stratified by age or the presence of CHF, CKD or atherosclerotic cardiovascular disease (ASCVD), are also currently lacking.Methods We searched the PubMed, Embase and Cochrane databases for relevant studies published up until 5 December 2020. RCTs comparing SGLT2i, GLP-1RA and DPP-4i with placebo (or other controls) or with each other with cardiovascular (CV) or renal outcomes were eligible for inclusion. The primary efficacy endpoint was 3-point major adverse cardiovascular events (3P-MACE), which are defined as CV death, non-fatal myocardial infarction and non-fatal ischaemic stroke. All-cause mortality, hospitalisation for heart failure (HHF) and composite renal outcomes were also analysed. Pre-specified subgroup analyses of 3P-MACE were also performed.Results A total of 21 trials with 170,930 participants were included in this network meta-analysis. Both GLP-1RA and SGLT2i were associated with lower risks of 3P-MACE than placebo (RR 0.89, 95% CI 0.84, 0.94 and RR 0.88, 95% CI 0.83, 0.94, respectively). GLP-1RA and SGLT2i were also associated with lower risks of 3P-MACE than DPP-4i (RR 0.89, 95% CI 0.82, 0.98 and RR 0.89, 95% CI 0.81, 0.97, respectively). A comparison between SGLT2i and GLP-1RA demonstrated no difference in their risks of 3P-MACE (RR 0.99, 95% CI 0.91, 1.08). Only GLP-1RA was associated with a lower risk of stroke compared with placebo (RR 0.85, 95% CI 0.76, 0.94). SGLT2i is superior to GLP-1RA in reducing HHF (RR 0.76, 95% CI 0.68, 0.84) and renal outcomes (RR 0.78.95% CI 0.65. 0.93). Subgroup analyses indicated that the benefits of SGLT2i and GLP-1RA were more pronounced in elderly patients, white and Asian patients, those with established ASCVD and those with longer durations of diabetes mellitus and worse glycaemic control.Conclusions/interpretation SGLT2i and GLP-1RA are superior to DPP-4i in terms of CV and renal outcomes. GLP-1RA is the only drug class that reduces the risk of stroke. SGLT2i is superior in reducing HHF and renal outcomes. Therefore, the choice between SGLT2i and GLP-1RA should be individualised according to patient profiles.