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. This study is based on data from the Clinical Practice Research Datalink obtained under license from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the UK National Health Service as part of their care and support. The interpretation and conclusions contained in this study are those of the authors alone. Because electronic health records are classified as “sensitive data” by the UK Data Protection Act, information governance restrictions (to protect patient confidentiality) prevent data sharing via public deposition. Data are available with approval, through the individual constituent entities controlling access to the data. Specifically, the primary care data can be requested via application to the Clinical Practice Research Datalink ().

中文翻译：

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胰高血糖素样肽 1 受体激动剂和钠-葡萄糖协同转运蛋白 2 抑制剂联合治疗对心血管和严重肾脏事件发生率的影响：基于人群的队列研究


目的 确定联合使用胰高血糖素样肽 1 (GLP-1) 受体激动剂和钠-葡萄糖协同转运蛋白 2 (SGLT-2) 抑制剂是否与降低主要不良心血管事件和严重肾脏事件的风险相关。在 2 型糖尿病患者中单独使用任一药物类别，并评估联合用药对主要不良心血管事件、心力衰竭和全因死亡率的各个组成部分的影响。使用流行的新用户设计来模拟试验，设计基于人群的队列研究。设置与医院情节统计承认的患者护理和国家统计办公室数据库链接的英国临床实践研究数据链接。参与者 2013 年 1 月至 2020 年 12 月期间聚集了两个流行的新用户队列，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，第二组包括 8942 名开始使用 SGLT-2 抑制剂并添加 GLP-1 受体激动剂的患者。组合使用者以 1:1 的比例与处方相同背景药物、背景药物持续时间和时间条件倾向评分的患者进行匹配。主要结果指标 采用 Cox 比例风险模型来分别评估主要不良心血管事件和严重肾脏事件的风险比和 95% 置信区间，将 GLP-1 受体激动剂 - SGLT-2 抑制剂组合与背景药物进行比较，或者GLP-1 受体激动剂或 SGLT-2 抑制剂，取决于队列。 次要结局包括与主要不良心血管事件（心肌梗塞、缺血性中风、心血管死亡率）、心力衰竭和全因死亡率的各个组成部分的关联。结果 与 GLP-1 受体激动剂相比，SGLT-2 抑制剂-GLP-1 受体激动剂组合的主要不良心血管事件风险降低 30%（每 1000 人年 7.0 比 10.3 次事件；风险比 0.70, 95%）置信区间 0.49 至 0.99），严重肾脏事件的风险降低 57%（每 1000 人年 2.0 比 4.6 次事件；风险比 0.43、0.23 至 0.80）。与 SGLT-2 抑制剂相比，GLP-1 受体激动剂-SGLT-2 抑制剂组合的主要不良心血管事件风险降低 29%（每 1000 人年 7.6 比 10.7 次事件；风险比 0.71、0.52 至 0.98） ，而严重的肾脏事件产生了广泛的置信区间（每 1000 人年 1.4 v 2.0 次事件；风险比 0.67、0.32 至 1.41）。次要结果产生了类似的结果，但置信区间更宽。结论 在这项队列研究中，与单独使用任一药物类别相比，GLP-1 受体激动剂 - SGLT-2 抑制剂组合与主要不良心血管事件和严重肾脏事件的风险较低相关。本研究基于经英国药品和保健产品监管机构许可获得的临床实践研究数据链的数据。这些数据由患者提供，并由英国国家卫生服务中心收集，作为其护理和支持的一部分。本研究中包含的解释和结论仅属于作者本人。 由于电子健康记录被英国数据保护法归类为“敏感数据”，信息治理限制（以保护患者机密）阻止通过公开存储进行数据共享。数据可通过控制数据访问的各个组成实体获得批准。具体来说，可以通过申请临床实践研究数据链接（ ）。