Rationale: Patients with chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D) have worse clinical outcomes compared with patients without metabolic dysregulation. GLP-1 (glucagon-like peptide 1) receptor agonists (GLP-1RAs) reduce asthma exacerbation risk and improve FVC in patients with COPD. Objectives: To determine whether GLP-1RA use is associated with reduced COPD exacerbation rates, and severe and moderate exacerbation risk, compared with other T2D therapies. Methods: A retrospective, observational, electronic health records-based study was conducted using an active comparator, new-user design of 1,642 patients with COPD in a U.S. health system from 2012 to 2022. The COPD cohort was identified using a previously validated machine learning algorithm that includes a natural language processing tool. Exposures were defined as prescriptions for GLP-1RAs (reference group), DPP-4 (dipeptidyl peptidase 4) inhibitors (DPP-4is), SGLT2 (sodium-glucose cotransporter 2) inhibitors, or sulfonylureas. Measurements and Main Results: Unadjusted COPD exacerbation counts were lower in GLP-1RA users. Adjusted exacerbation rates were significantly higher in DPP-4i (incidence rate ratio, 1.48 [95% confidence interval, 1.08-2.04]; P = 0.02) and sulfonylurea (incidence rate ratio, 2.09 [95% confidence interval, 1.62-2.69]; P < 0.0001) users compared with GLP-1RA users. GLP-1RA use was also associated with significantly reduced risk of severe exacerbations compared with DPP-4i and sulfonylurea use, and of moderate exacerbations compared with sulfonylurea use. After adjustment for clinical covariates, moderate exacerbation risk was also lower in GLP-1RA users compared with DPP-4i users. No statistically significant difference in exacerbation outcomes was seen between GLP-1RA and SGLT2 inhibitor users. Conclusions: Prospective studies of COPD exacerbations in patients with comorbid T2D are warranted. Additional research may elucidate the mechanisms underlying these observed associations with T2D medications.

中文翻译：

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GLP-1 受体激动剂与 2 型糖尿病患者慢性阻塞性肺疾病恶化的关联。

理由：与没有代谢失调的患者相比，慢性阻塞性肺疾病 (COPD) 和 2 型糖尿病 (T2D) 患者的临床结果更差。GLP-1（胰高血糖素样肽 1）受体激动剂 (GLP-1RA) 可降低慢性阻塞性肺病患者的哮喘恶化风险并改善 FVC。目的：确定与其他 T2D 疗法相比，GLP-1RA 的使用是否与降低 COPD 恶化率以及重度和中度恶化风险相关。方法：使用主动比较器、新用户设计对 2012 年至 2022 年美国卫生系统中 1,642 名 COPD 患者进行了一项基于电子健康记录的回顾性、观察性研究。COPD 队列是使用先前验证的机器学习来识别的包含自然语言处理工具的算法。暴露定义为 GLP-1RA（参考组）、DPP-4（二肽基肽酶 4）抑制剂（DPP-4is）、SGLT2（钠-葡萄糖协同转运蛋白 2）抑制剂或磺酰脲类药物的处方。测量和主要结果：GLP-1RA 用户中未经调整的 COPD 恶化计数较低。DPP-4i（发生率比，1.48 [95% 置信区间，1.08-2.04]；P = 0.02）和磺酰脲类（发生率比，2.09 [95% 置信区间，1.62-2.69]）调整后的恶化率显着较高； P < 0.0001) 用户与 GLP-1RA 用户相比。与使用 DPP-4i 和磺酰脲类相比，使用 GLP-1RA 还可以显着降低严重急性加重的风险，与使用磺酰脲类相比，可以显着降低中度急性加重的风险。调整临床协变量后，与 DPP-4i 用户相比，GLP-1RA 用户中度恶化风险也较低。GLP-1RA 和 SGLT2 抑制剂使用者之间的恶化结果没有统计学上的显着差异。结论：有必要对合并 T2D 患者的 COPD 加重进行前瞻性研究。其他研究可能会阐明这些观察到的与 T2D 药物关联的机制。