根据 2 型糖尿病患者的虚弱情况比较 SGLT-2 抑制剂、GLP-1 受体激动剂和 DPP-4 抑制剂的心血管有效性和安全性。
Comparative Cardiovascular Effectiveness and Safety of SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors According to Frailty in Type 2 Diabetes.
机构信息
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
Marcus Institute for Aging Research, Hebrew SeniorLife, Boston, MA.
出版信息
Diabetes Care. 2023 Nov 1;46(11):2004-2014. doi: 10.2337/dc23-0671.
OBJECTIVE
To evaluate the comparative cardiovascular effectiveness and safety of sodium-glucose cotransporter 2 inhibitors (SGLT-2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and dipeptidyl peptidase 4 inhibitors (DPP-4is) in older adults with type 2 diabetes (T2D) across different frailty strata.
RESEARCH DESIGN AND METHODS
We performed three 1:1 propensity score-matched cohort studies, each stratified by three frailty strata, using data from Medicare beneficiaries (2013-2019) with T2D who initiated SGLT-2is, GLP-1RAs, or DPP-4is. In time-to-event analyses, we assessed the primary cardiovascular effectiveness composite outcome of acute myocardial infarction, ischemic stroke, hospitalization for heart failure, and all-cause mortality. The primary safety outcome was a composite of severe adverse events that have been linked to SGLT-2i or GLP-1RA use.
RESULTS
Compared with DPP-4is, the overall hazard ratio (HR) for the primary effectiveness outcome associated with SGLT-2is (n = 120,202 matched pairs) was 0.72 (95% CI 0.69-0.75), corresponding to an incidence rate difference (IRD) of -13.35 (95% CI -15.06 to -11.64). IRD ranged from -6.74 (95% CI -8.61 to -4.87) in nonfrail to -27.24 (95% CI -41.64 to -12.84) in frail people (P for interaction < 0.01). Consistent benefits were observed for GLP-1RAs compared with DPP-4is (n = 113,864), with an overall HR of 0.74 (95% CI 0.71-0.77) and an IRD of -15.49 (95% CI -17.46 to -13.52). IRD in the lowest frailty stratum was -7.02 (95% CI -9.23 to -4.81) and -25.88 (95% CI -38.30 to -13.46) in the highest (P for interaction < 0.01). Results for SGLT-2is versus GLP-1RAs (n = 89,865) were comparable. Severe adverse events were not more frequent with SGLT-2is or GLP-1RAs than DPP-4is.
CONCLUSIONS
SGLT-2is and GLP-1RAs safely improved cardiovascular outcomes and all-cause mortality, with the largest absolute benefits among frail people.
目的
评估钠-葡萄糖协同转运蛋白 2 抑制剂（SGLT-2i）、胰高血糖素样肽 1 受体激动剂（GLP-1RA）和二肽基肽酶 4 抑制剂（DPP-4i）在不同虚弱分层的老年 2 型糖尿病（T2D）患者中的心血管比较疗效和安全性。
研究设计和方法
我们使用了 Medicare 受益人的数据（2013-2019 年），进行了三项 1:1 倾向评分匹配队列研究，每个研究都按三个虚弱分层进行分层，这些患者开始使用 SGLT-2i、GLP-1RA 或 DPP-4i。在时间事件分析中，我们评估了急性心肌梗死、缺血性中风、心力衰竭住院和全因死亡率的主要心血管有效性复合结局。主要安全性结局是与 SGLT-2i 或 GLP-1RA 使用相关的严重不良事件的复合。
结果
与 DPP-4i 相比，SGLT-2i（n = 120,202 匹配对）与主要有效性结局相关的总体危险比（HR）为 0.72（95%CI 0.69-0.75），对应的发病率差异（IRD）为-13.35（95%CI-15.06 至-11.64）。IRD 范围从非虚弱患者的-6.74（95%CI-8.61 至-4.87）到虚弱患者的-27.24（95%CI-41.64 至-12.84）（P 交互<0.01）。与 DPP-4i 相比，GLP-1RA 也观察到一致的益处（n = 113,864），总 HR 为 0.74（95%CI 0.71-0.77），IRD 为-15.49（95%CI-17.46 至-13.52）。在最低虚弱分层中，IRD 为-7.02（95%CI-9.23 至-4.81），在最高虚弱分层中为-25.88（95%CI-38.30 至-13.46）（P 交互<0.01）。SGLT-2i 与 GLP-1RA（n = 89,865）的结果相当。SGLT-2i 或 GLP-1RA 并不比 DPP-4i 更频繁地发生严重不良事件。
结论
SGLT-2i 和 GLP-1RA 安全地改善了心血管结局和全因死亡率，在虚弱患者中获益最大。
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