Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects. Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58–0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45–0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53–0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78–0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72–0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region. This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614

中文翻译：

---

三大洲 13 个国家的钠-葡萄糖协同转运蛋白 2 抑制剂与其他降糖药物的心血管结局：CVD-REAL 数据分析

随机、受控的心血管结局试验可能不能完全代表不同地理区域的 2 型糖尿病患者的管理。我们对来自多国 CVD-REAL 联盟的数据进行了分析，以确定钠-葡萄糖协同转运蛋白 2 抑制剂 (SGLT-2i) 的启动与心血管结局之间的关联，包括基于患者特征的亚组分析。来自三大洲 13 个国家的去识别化健康记录被用于识别新开始使用 SGLT-2i 或其他降糖药 (oGLDs) 的患者。每个国家都制定了 SGLT-2i 启动的倾向评分，oGLD 启动的匹配率为 1:1。在匹配组中因心力衰竭 (HHF)、全因死亡 (ACD)、HHF 或 ACD 的复合住院的风险比 (HR)，心肌梗塞 (MI) 和中风按国家/地区估算，并使用加权荟萃分析汇总。跨患者人口统计学和临床​​特征进行了多个亚组分析，以检查治疗效果的任何异质性。匹配后，每组包括 440,599 名 SGLT-2i 和 oGLD 的新用户。SGLT-2i 启动的平均随访时间为 396 天，oGLDs 启动的平均随访时间为 406 天。SGLT-2i 启动与较低的 HHF 风险相关（HR：0.66，95%CI 0.58–0.75；p < 0.001），ACD（HR：0.52，95%CI 0.45–0.60；p < 0.001），复合HHF 或 ACD（HR：0.60，95%CI 0.53–0.68；p < 0.001），MI（HR：0.85，95%CI 0.78–0.92；p < 0.001）和中风（HR：0.78，95%CI 0.72） 0.85；p < 0.001)；无论患者的特征如何，包括已确诊的心血管疾病，或地理区域。这项 CVD-REAL 研究将 SGLT-2i 临床试验的结果扩展到更广泛的种族和地理多样化人群以及多个亚组。试用注册 NCT02993614