Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
Department of Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China.
JAMA Netw Open. 2023 Jan 3;6(1):e2251177. doi: 10.1001/jamanetworkopen.2022.51177.
Patients with diabetes are at higher risk for obstructive airway disease (OAD). In recent meta-analyses of post hoc analyses of cardiorenal trials, sodium-glucose cotransporter 2 inhibitors (SGLT2Is) were suggested to reduce the risk of OAD adverse events. However, a clinical investigation of this association is warranted.
This study aimed to investigate the association of SGLT2I use vs dipeptidyl peptidase-4 inhibitor (DPP4I) use with OAD incidence and exacerbation events in patients with type 2 diabetes.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective population-based cohort study used electronic health data from a territory-wide electronic medical database in Hong Kong. Data were collected for patients with type 2 diabetes who were prescribed SGLT2Is or DPP4Is between January 1, 2015, and December 31, 2018. Patients were followed for a median of 2.2 years between January 1, 2015, and December 31, 2020. A prevalent new-user design was adopted to match patients based on previous exposure to the study drugs. Propensity score matching was used to balance baseline characteristics.
Patients with type 2 diabetes using SGLT2Is (exposure of interest) or DPP4Is (active comparator).
The main outcomes were the first incidence of OAD and the count of OAD exacerbations. The risk of incident OAD was estimated using a Cox proportional hazards regression model. The rate of exacerbations was estimated using zero-inflated Poisson regression. Statistical analysis was performed on November 13, 2022.
This study included 30 385 patients. The propensity score-matched non-OAD cohort (incidence analysis) consisted of 5696 SGLT2I users and 22 784 DPP4I users, while the matched OAD cohort (exacerbations analysis) comprised 381 SGLT2I users and 1524 DPP4I users. At baseline, 56% of patients in the non-OAD cohort were men and the mean (SD) age was 61.2 (9.9) years; 51% of patients in the OAD cohort were men and the mean age was 62.2 (10.8) years. Compared with DPP4I use, SGLT2I use was associated with a lower risk of incident OAD (hazard ratio, 0.65 [95% CI, 0.54-0.79]; P < .001) and a lower rate of exacerbations (rate ratio, 0.54 [95% CI, 0.36-0.83]; P = .01). The associations were consistent in sex subgroup analysis.
The findings of this retrospective cohort study of patients with type 2 diabetes in Hong Kong suggest that SGLT2I use was associated with a reduced risk of incident OAD and a lower rate of exacerbations in a clinical setting compared with DPP4I use. These findings further suggest that SGLT2Is may provide additional protective effects against OAD for patients with type 2 diabetes and that further investigation is warranted.
患有糖尿病的患者发生阻塞性气道疾病（OAD）的风险更高。在最近对心脏肾脏试验的事后分析的荟萃分析中，提示钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2Is）可降低 OAD 不良事件的风险。然而，有必要对此关联进行临床研究。
本研究旨在调查 SGLT2I 与二肽基肽酶-4 抑制剂（DPP4I）的使用与 2 型糖尿病患者 OAD 发病和加重事件的关系。
设计、设置和参与者：这是一项回顾性基于人群的队列研究，使用了香港全地域电子病历数据库中的电子健康数据。数据收集了 2015 年 1 月 1 日至 2018 年 12 月 31 日期间接受 SGLT2Is 或 DPP4Is 治疗的 2 型糖尿病患者。在 2020 年 12 月 31 日，患者接受了中位 2.2 年的随访。采用现患新用户设计，根据患者之前对研究药物的暴露情况进行匹配。使用倾向评分匹配来平衡基线特征。
使用 SGLT2Is（感兴趣的暴露）或 DPP4Is（活性对照）的 2 型糖尿病患者。
主要结局是 OAD 的首次发病和 OAD 加重的次数。使用 Cox 比例风险回归模型估计 OAD 发病风险。使用零膨胀泊松回归估计加重率。统计分析于 2022 年 11 月 13 日进行。
这项研究纳入了 30385 名患者。未发生 OAD 的倾向评分匹配队列（发病分析）包括 5696 名 SGLT2I 用户和 22784 名 DPP4I 用户，而发生 OAD 的匹配队列（加重分析）包括 381 名 SGLT2I 用户和 1524 名 DPP4I 用户。在基线时，非 OAD 队列中 56%的患者为男性，平均（SD）年龄为 61.2（9.9）岁；OAD 队列中 51%的患者为男性，平均年龄为 62.2（10.8）岁。与 DPP4I 相比，SGLT2I 的使用与 OAD 的发病风险降低相关（风险比，0.65[95%CI，0.54-0.79]；P < 0.001），并且与较低的加重率相关（率比，0.54[95%CI，0.36-0.83]；P = 0.01）。在性别亚组分析中，结果一致。
这项在香港开展的 2 型糖尿病患者的回顾性队列研究表明，与 DPP4I 相比，SGLT2I 的使用与 OAD 发病风险降低和临床环境中加重率降低相关。这些发现进一步表明，SGLT2Is 可能为 2 型糖尿病患者提供 OAD 的额外保护作用，需要进一步研究。
