加拿大蒙特利尔犹太总医院Laurent Azoulay团队研究了胰高血糖素样肽-1（GLP-1）受体激动剂和钠-葡萄糖协同转运蛋白-2（SGLT-2）抑制剂联合使用对2型糖尿病患者预后的影响。这一研究成果发表在2024年4月25日出版的《英国医学杂志》上。

为了确定在2型糖尿病患者中，与单独使用任一药物类别相比，胰高血糖素样肽-1（GLP-1）受体激动剂和钠-葡萄糖协同转运蛋白-2（SGLT-2）抑制剂的联合使用是否与重大心血管不良事件和严重肾事件的风险降低有关，并评估联合使用对重大心血管不良反应、心力衰竭和全因死亡率的单个成分的影响，研究组进行了一项基于人群的队列研究，使用流行的新用户设计来模拟试验。

该研究使用英国临床实践研究数据链接，链接到医院事件统计入院患者护理和国家统计局数据库。2013年1月至2020年12月，研究组收集了两个流行的新用户群体，并随访至2021年3月底。第一个队列包括6696名开始使用GLP-1受体激动剂并添加SGLT-2抑制剂的患者，第二个队列包括8942名开始使用SGLT-2抑制剂并添加GLP-1受体激动剂的患者。联合用药者以1:1的比例与服用相同背景药物的患者、背景药物的持续时间和时间条件倾向评分相匹配。

使用拟合Cox比例风险模型来分别估计重大不良心血管事件和严重肾脏事件的风险比和95%置信区间，根据队列将GLP-1受体激动剂-SGLT-2抑制剂组合与背景药物GLP-1受体激动剂或SGLT-2抑制剂进行比较。次要结局包括与重大不良心血管事件（心肌梗死、缺血性中风、心血管死亡率）、心力衰竭和全因死亡率的个体组成部分的相关性。

与GLP-1受体激动剂相比，SGLT-2抑制剂-GLP-1受体激动剂组合的重大不良心血管事件风险降低30%（每1000人-年7.0比10.3事件；危险比0.70，95%置信区间0.49至0.99），严重肾脏事件风险降低57%（每1000人-年2.0比4.6事件；危险比为0.43，0.23至0.80）。与SGLT-2抑制剂相比，GLP-1受体激动剂-SGLT-2抑制剂组合的重大不良心血管事件风险降低29%（每1000人-年7.6比10.7事件；危险比为0.71，0.52比0.98），而严重肾脏事件产生的置信区间较宽（每1000人-年1.4比2.0事件；危险比为0.67，0.32比1.41）。次要结局产生了相似的结果，但置信区间更宽。

研究结果表明，在这项队列研究中，与单独的任一药物类别相比，GLP-1受体激动剂-SGLT-2抑制剂组合与较低的重大不良心血管事件和严重肾脏事件风险相关。

附：英文原文

Title: Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study

Author: Nikita Simms-Williams, Nir Treves, Hui Yin, Sally Lu, Oriana Yu, Richeek Pradhan, Christel Renoux, Samy Suissa, Laurent Azoulay

Issue&Volume: 2024/04/25

Abstract:

Objective To determine whether the combined use of glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors is associated with a decreased risk of major adverse cardiovascular events and serious renal events compared with either drug class alone among patients with type 2 diabetes, and to assess the effect of the combination on the individual components of major adverse cardiovascular events, heart failure, and all cause mortality.

Design Population based cohort study using a prevalent new-user design, emulating a trial.

Setting UK Clinical Practice Research Datalink linked to Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases.

Participants Two prevalent new-user cohorts were assembled between January 2013 and December 2020, with follow-up until the end of March 2021. The first cohort included 6696 patients who started GLP-1 receptor agonists and added on SGLT-2 inhibitors, and the second included 8942 patients who started SGLT-2 inhibitors and added on GLP-1 receptor agonists. Combination users were matched, in a 1:1 ratio, to patients prescribed the same background drug, duration of background drug, and time conditional propensity score.

Main outcome measures Cox proportional hazards models were fitted to estimate the hazard ratios and 95% confidence intervals of major adverse cardiovascular events and serious renal events, separately, comparing the GLP-1 receptor agonist-SGLT-2 inhibitor combination with the background drug, either GLP-1 receptor agonists or SGLT-2 inhibitors, depending on the cohort. Secondary outcomes included associations with the individual components of major adverse cardiovascular events (myocardial infarction, ischaemic stroke, cardiovascular mortality), heart failure, and all cause mortality.

Results Compared with GLP-1 receptor agonists, the SGLT-2 inhibitor-GLP-1 receptor agonist combination was associated with a 30% lower risk of major adverse cardiovascular events (7.0 v 10.3 events per 1000 person years; hazard ratio 0.70, 95% confidence interval 0.49 to 0.99) and a 57% lower risk of serious renal events (2.0 v 4.6 events per 1000 person years; hazard ratio 0.43, 0.23 to 0.80). Compared with SGLT-2 inhibitors, the GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a 29% lower risk of major adverse cardiovascular events (7.6 v 10.7 events per 1000 person years; hazard ratio 0.71, 0.52 to 0.98), whereas serious renal events generated a wide confidence interval (1.4 v 2.0 events per 1000 person years; hazard ratio 0.67, 0.32 to 1.41). Secondary outcomes generated similar results but with wider confidence intervals.

Conclusions In this cohort study, the GLP-1 receptor agonist-SGLT-2 inhibitor combination was associated with a lower risk of major adverse cardiovascular events and serious renal events compared with either drug class alone.

DOI: 10.1136/bmj-2023-078242

Source: https://www.bmj.com/content/385/bmj-2023-078242