Meng Lin-Chieh, Chuang Hui-Min, Lai Hsi-Yu, Chen Ho-Min, Yang Kuang-Yao, Chen Liang-Kung, Hsiao Fei-Yuan
Health Data Research Center, National Taiwan University, Taipei, Taiwan.
Graduate Institute of Clinical Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
EClinicalMedicine. 2025 Jul 3;85:103332. doi: 10.1016/j.eclinm.2025.103332. eCollection 2025 Jul.
BACKGROUND: The coexistence of type 2 diabetes (T2D) and chronic obstructive pulmonary disease (COPD) poses significant clinical challenges, particularly in aging populations. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) show promise for pulmonary protection, their effectiveness compared to other newer antidiabetic agents across different frailty levels remains unknown. METHODS: In this population-based cohort study using Taiwan's National Health Insurance database, we identified adults aged ≥40 years with coexisting T2D and COPD who initiated SGLT2i or comparator drugs (dipeptidyl peptidase-4 inhibitors [DPP-4i] or glucagon-like peptide-1 receptor agonists [GLP-1 RA]) between January 1, 2017, and December 31, 2020. We classified participants overall and stratified by frailty status using the multimorbidity frailty index. After propensity score matching, we estimated subdistribution hazard ratios (sHR) and incidence rate differences (IRD) for a composite pulmonary endpoint (first hospitalization for COPD exacerbation or pneumonia) and for each outcome separately, with follow-up through December 31, 2021. We also assessed all-cause hospitalization and all-cause mortality as secondary outcomes. FINDINGS: Among 14,787 propensity-score-matched pairs of SGLT2i versus DPP-4i users (7606 fit/mild, 3834 moderate, 3347 severe frailty), SGLT2i use was associated with a lower risk of the composite pulmonary endpoint (sHR 0.83 [95% CI 0.77-0.90]; IRD -28.0 per 1000 person-years [95% CI -36.0 to -20.0]), a reduced risk of COPD hospitalization in the fit/mild subgroup (sHR 0.82 [0.69-0.98]), decreased pneumonia hospitalization across all frailty strata (sHR range 0.65-0.85), and lower risks of all-cause hospitalization (sHR 0.91 [0.86-0.95]) and all-cause mortality (sHR 0.60 [0.53-0.68]). In 4815 matched SGLT2i versus GLP-1RA pairs (2101 fit/mild, 1294 moderate, 1420 severe frailty), SGLT2i use showed no significant differences for any outcomes. INTERPRETATION: Compared with DPP-4i, SGLT2i reduced the composite pulmonary endpoint overall, prevented COPD hospitalizations primarily in fit or mildly frail patients, and conferred protection against pneumonia admissions across most frailty strata, while showing comparable benefits to GLP-1 RA. These findings suggest that both SGLT2i and GLP-1 RA may be preferred options for T2D patients with COPD, with effectiveness influenced by frailty status. FUNDING: National Science and Technology Council, Taiwan.
背景:2型糖尿病(T2D)与慢性阻塞性肺疾病(COPD)并存给临床带来了重大挑战,在老年人群中尤为如此。虽然钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)显示出对肺部有保护作用,但与其他新型抗糖尿病药物相比,其在不同虚弱程度人群中的有效性尚不清楚。 方法:在这项基于人群的队列研究中,我们使用台湾国民健康保险数据库,确定了2017年1月1日至2020年12月31日期间开始使用SGLT2i或对照药物(二肽基肽酶-4抑制剂[DPP-4i]或胰高血糖素样肽-1受体激动剂[GLP-1 RA])的40岁及以上同时患有T2D和COPD的成年人。我们对参与者进行总体分类,并使用多病共存虚弱指数按虚弱状态进行分层。在倾向得分匹配后,我们估计了复合肺部终点(因COPD加重或肺炎首次住院)以及每个结局单独的亚分布风险比(sHR)和发病率差异(IRD),随访至2021年12月31日。我们还将全因住院和全因死亡率作为次要结局进行评估。 结果:在14787对倾向得分匹配的SGLT2i与DPP-4i使用者中(7606例健康/轻度虚弱、3834例中度虚弱、3347例重度虚弱),使用SGLT2i与复合肺部终点风险较低相关(sHR 0.83[9
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