Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are treatments for type 2 diabetes (T2D). Beyond glucose-lowering and cardiorenal protection, these drugs may protect against pneumonia and sepsis. Aims This study assesses the impact of SGLT2i and GLP-1 RAs on the risk of incident pneumonia and severe sepsis. Methods A retrospective cohort study was conducted using anonymised electronic medical records from TriNetX, a global federated database. Two intention-to-treat analyses were performed, each with two cohorts of adult T2D patients. The first analysis compared individuals prescribed SGLT2i, and the second individuals prescribed GLP-1 RAs, with those prescribed dipeptidyl peptidase-4 inhibitors (DPP-4i). An active comparator new user design was used, with outcomes defined as time-to-incident pneumonia and severe sepsis. Propensity score matching (1:1) was applied to control for potential confounders, and patients were followed for 12 months. Secondary analyses compared SGLT2i and GLP-1 RAs against other glucose-lowering therapies. Results After propensity score matching, 352 687 patients were included in the SGLT2i versus DPP-4i comparison. SGLT2i treatment was associated with a risk reduction in incident pneumonia (HR 0.75 (95% CI 0.73, 0.78)) and severe sepsis (0.75 (0.73, 0.77)). In the GLP-1 RA versus DPP-4i comparison, 331 863 patients were included. GLP-1 RA treatment was associated with a risk reduction in incident pneumonia (0.60 (0.58, 0.62)) and severe sepsis (0.61 (0.59, 0.63)). Conclusion SGLT2i and GLP-1 RAs are associated with a reduced risk of incident pneumonia and severe sepsis in patients with T2D. Further research and focused randomised controlled trials are warranted to explore the broader clinical implications of these treatments. Data may be obtained from a third party and are not publicly available. The data that support the findings of this study are available from TriNetX, LLC, , but third-party restrictions apply to the availability of these data. The data were used under license for this study with restrictions that do not allow for the data to be redistributed or made publicly available. However, for accredited researchers, the TriNetX data are available for licensing at TriNetX, LLC. Data access may require a data sharing agreement and may incur data access fees. Data used in the generation of this paper was collected from the global TriNetX network and local data at LUHFT were not used.

中文翻译：

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降糖疗法对肺炎和严重败血症风险的比较估计：真实世界队列数据分析


背景钠-葡萄糖协同转运蛋白-2 抑制剂 （SGLT2i） 和胰高血糖素样肽-1 受体激动剂 （GLP-1 RAs） 是 2 型糖尿病 （T2D） 的治疗方法。除了降低血糖和保护心肾外，这些药物还可以预防肺炎和脓毒症。目的 本研究评估 SGLT2i 和 GLP-1 RAs 对肺炎和严重败血症风险的影响。方法 使用来自全球联合数据库 TriNetX 的匿名电子病历进行了一项回顾性队列研究。进行了两项意向性治疗分析，每项分析有两组成年 T2D 患者。第一项分析将开具 SGLT2i 的个体，第二种开具 GLP-1 RAs 的个体与开具二肽基肽酶-4 抑制剂 （DPP-4i） 的个体进行了比较。使用主动对照新用户设计，结局定义为事件发生时间肺炎和严重败血症。倾向评分匹配 （1：1） 用于控制潜在的混杂因素，并对患者进行了 12 个月的随访。二次分析将 SGLT2i 和 GLP-1 RAs 与其他降糖疗法进行了比较。结果 倾向评分匹配后，SGLT2i 与 DPP-4i 比较纳入 352 687 例患者。SGLT2i 治疗与新发肺炎 （HR 0.75 （95% CI 0.73， 0.78）） 和严重脓毒症 （0.75 （0.73， 0.77）） 的风险降低相关。在 GLP-1 RA 与 DPP-4i 的比较中，共纳入 331 863 例患者。GLP-1 RA 治疗与新发肺炎 （0.60 （0.58， 0.62）） 和重症脓毒症 （0.61 （0.59， 0.63） 的风险降低相关。结论 SGLT2i 和 GLP-1 RAs 与 T2D 患者发生肺炎和重症脓毒症的风险降低相关。 有必要进行进一步的研究和重点随机对照试验，以探索这些治疗的更广泛的临床意义。数据可能从第三方获得，并且不会公开。支持本研究结果的数据可从 TriNetX， LLC 获得，但这些数据的可用性受第三方限制。这些数据是在本研究的许可下使用的，但有限制，不允许重新分发或公开数据。但是，对于经过认证的研究人员，TriNetX 数据可在 TriNetX， LLC 获得许可。数据访问可能需要数据共享协议，并可能产生数据访问费用。用于生成本文的数据是从全球 TriNetX 网络收集的，未使用 LUHFT 的本地数据。