PDF(Pubmed)
Abstract：
UNASSIGNED: SGLT2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1-RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head trials.
UNASSIGNED: Across the LEGEND-T2DM network, we included ten federated international data sources, spanning 1992-2021. We identified 1,492,855 patients with T2DM and established cardiovascular disease (CVD) on metformin monotherapy who initiated one of four second-line agents (SGLT2is, GLP1-RAs, dipeptidyl peptidase 4 inhibitor [DPP4is], sulfonylureas [SUs]). We used large-scale propensity score models to conduct an active comparator, target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, we fit on-treatment Cox proportional hazard models for 3-point MACE (myocardial infarction, stroke, death) and 4-point MACE (3-point MACE + heart failure hospitalization) risk, and combined hazard ratio (HR) estimates in a random-effects meta-analysis.
UNASSIGNED: Across cohorts, 16·4%, 8·3%, 27·7%, and 47·6% of individuals with T2DM initiated SGLT2is, GLP1-RAs, DPP4is, and SUs, respectively. Over 5·2 million patient-years of follow-up and 489 million patient-days of time at-risk, there were 25,982 3-point MACE and 41,447 4-point MACE events. SGLT2is and GLP1-RAs were associated with a lower risk for 3-point MACE compared with DPP4is (HR 0·89 [95% CI, 0·79-1·00] and 0·83 [0·70-0·98]), and SUs (HR 0·76 [0·65-0·89] and 0·71 [0·59-0·86]). DPP4is were associated with a lower 3-point MACE risk versus SUs (HR 0·87 [0·79-0·95]). The pattern was consistent for 4-point MACE for the comparisons above. There were no significant differences between SGLT2is and GLP1-RAs for 3-point or 4-point MACE (HR 1·06 [0·96-1·17] and 1·05 [0·97-1·13]).
UNASSIGNED: In patients with T2DM and established CVD, we found comparable cardiovascular risk reduction with SGLT2is and GLP1-RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of GLP1-RAs and SGLT2is should be prioritized as second-line agents in those with established CVD.
UNASSIGNED: National Institutes of Health, United States Department of Veterans Affairs.
UNASSIGNED: Across the LEGEND-T2DM network, we included ten federated international data sources, spanning 1992-2021. We identified 1,492,855 patients with T2DM and established cardiovascular disease (CVD) on metformin monotherapy who initiated one of four second-line agents (SGLT2is, GLP1-RAs, dipeptidyl peptidase 4 inhibitor [DPP4is], sulfonylureas [SUs]). We used large-scale propensity score models to conduct an active comparator, target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, we fit on-treatment Cox proportional hazard models for 3-point MACE (myocardial infarction, stroke, death) and 4-point MACE (3-point MACE + heart failure hospitalization) risk, and combined hazard ratio (HR) estimates in a random-effects meta-analysis.
UNASSIGNED: Across cohorts, 16·4%, 8·3%, 27·7%, and 47·6% of individuals with T2DM initiated SGLT2is, GLP1-RAs, DPP4is, and SUs, respectively. Over 5·2 million patient-years of follow-up and 489 million patient-days of time at-risk, there were 25,982 3-point MACE and 41,447 4-point MACE events. SGLT2is and GLP1-RAs were associated with a lower risk for 3-point MACE compared with DPP4is (HR 0·89 [95% CI, 0·79-1·00] and 0·83 [0·70-0·98]), and SUs (HR 0·76 [0·65-0·89] and 0·71 [0·59-0·86]). DPP4is were associated with a lower 3-point MACE risk versus SUs (HR 0·87 [0·79-0·95]). The pattern was consistent for 4-point MACE for the comparisons above. There were no significant differences between SGLT2is and GLP1-RAs for 3-point or 4-point MACE (HR 1·06 [0·96-1·17] and 1·05 [0·97-1·13]).
UNASSIGNED: In patients with T2DM and established CVD, we found comparable cardiovascular risk reduction with SGLT2is and GLP1-RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of GLP1-RAs and SGLT2is should be prioritized as second-line agents in those with established CVD.
UNASSIGNED: National Institutes of Health, United States Department of Veterans Affairs.
摘要：
■SGLT2抑制剂（SGLT2is）和GLP-1受体激动剂（GLP1-RA）可降低2型糖尿病（T2DM）患者的主要不良心血管事件（MACE）。然而,它们相对于彼此和其他二线降糖药的有效性是未知的，没有任何重大的正面交锋试验.
■跨LEGEND-T2DM网络，我们包括了十个联合的国际数据源，跨越1992-2021年。我们确定了1,492,855例使用二甲双胍单药治疗的T2DM和心血管疾病（CVD）患者，他们开始了四种二线药物之一（SGLT2is，GLP1-RA,二肽基肽酶4抑制剂[DPP4is]，磺酰脲类[SUs])。我们使用大规模倾向得分模型进行了主动比较，成对比较的目标试验仿真。在评估了经验均衡和种群普适性之后，我们拟合3点MACE的治疗Cox比例风险模型(心肌梗死，中风,死亡）和4点MACE（3点MACE+心力衰竭住院）风险，和随机效应荟萃分析中的综合风险比(HR)估计。
■跨队列，16·4%，8·3%，27·7%，47·6%的T2DM患者开始SGLT2is，GLP1-RA,DPP4is,和SUs，分别。超过500万患者年的随访时间和4.89亿患者天的风险时间，有25,982个3点MACE事件和41,447个4点MACE事件。与DPP4相比，SGLT2is和GLP1-RA与3点MACE的风险较低相关（HR0·89[95％CI，0·79-1·00]和0·83[0·70-0·98]），和SU（HR0·76[0·65-0·89]和0·71[0·59-0·86]）。与SUs相比，DPP4与较低的3点MACE风险相关（HR0·87[0·79-0·95]）。对于上述比较，4点MACE的模式是一致的。SGLT2is和GLP1-RAs在3点或4点MACE中没有显着差异（HR1·06[0·96-1·17]和1·05[0·97-1·13]）。
■在T2DM和已建立的CVD患者中，我们发现SGLT2is和GLP1-RAs可降低心血管风险，两种药物都比DPP4更有效，这反过来又比SUs更有效。这些发现表明，GLP1-RAs和SGLT2is的使用应优先作为已建立CVD的二线药物。
■美国国立卫生研究院,美国退伍军人事务部。
■跨LEGEND-T2DM网络，我们包括了十个联合的国际数据源，跨越1992-2021年。我们确定了1,492,855例使用二甲双胍单药治疗的T2DM和心血管疾病（CVD）患者，他们开始了四种二线药物之一（SGLT2is，GLP1-RA,二肽基肽酶4抑制剂[DPP4is]，磺酰脲类[SUs])。我们使用大规模倾向得分模型进行了主动比较，成对比较的目标试验仿真。在评估了经验均衡和种群普适性之后，我们拟合3点MACE的治疗Cox比例风险模型(心肌梗死，中风,死亡）和4点MACE（3点MACE+心力衰竭住院）风险，和随机效应荟萃分析中的综合风险比(HR)估计。
■跨队列，16·4%，8·3%，27·7%，47·6%的T2DM患者开始SGLT2is，GLP1-RA,DPP4is,和SUs，分别。超过500万患者年的随访时间和4.89亿患者天的风险时间，有25,982个3点MACE事件和41,447个4点MACE事件。与DPP4相比，SGLT2is和GLP1-RA与3点MACE的风险较低相关（HR0·89[95％CI，0·79-1·00]和0·83[0·70-0·98]），和SU（HR0·76[0·65-0·89]和0·71[0·59-0·86]）。与SUs相比，DPP4与较低的3点MACE风险相关（HR0·87[0·79-0·95]）。对于上述比较，4点MACE的模式是一致的。SGLT2is和GLP1-RAs在3点或4点MACE中没有显着差异（HR1·06[0·96-1·17]和1·05[0·97-1·13]）。
■在T2DM和已建立的CVD患者中，我们发现SGLT2is和GLP1-RAs可降低心血管风险，两种药物都比DPP4更有效，这反过来又比SUs更有效。这些发现表明，GLP1-RAs和SGLT2is的使用应优先作为已建立CVD的二线药物。
■美国国立卫生研究院,美国退伍军人事务部。
