加拿大麦吉尔大学Laurent Azoulay团队研究了新型抗高血糖药物预防2型糖尿病患者慢性阻塞性肺疾病加重的效果。相关论文于2022年11月1日发表在《英国医学杂志》上。

为了确定胰高血糖素样肽1（GLP-1）受体激动剂、二肽基肽酶4（DPP-4）抑制剂和钠-葡萄糖共转运蛋白2（SGLT-2）抑制剂的单独使用是否与慢性阻塞性肺病和2型糖尿病患者中慢性阻塞性肺病恶化风险的降低相关，研究组将英国临床实践研究数据与医院住院病例统计、住院病人护理和国家统计局的数据库相关联，进行了一项主动对照、新用户设计、基于人群的队列研究。

共有三个主动对照组，新型研究药物（GLP-1受体激动剂、DPP-4抑制剂或SGLT-2抑制剂）或磺酰脲类药物的有慢性阻塞性肺病史的患者队列。第一个队列包括1252名开始使用GLP-1受体激动剂的患者和14259名开始使用磺酰脲类药物的患者，第二个队列包括8731名开始使用DPP-4抑制剂的患者和18204名开始使用磺酸脲类药物的患者，第三个队列包括2956名开始使用SGLT-2抑制剂的患者以及10841名开始使用硫酸脲类药物的患者。

分别对GLP-1受体激动剂、DPP-4抑制剂和SGLT-2抑制剂组采用具有倾向评分精细分层加权的Cox比例风险模型来估计慢性阻塞性肺疾病（定义为慢性阻塞性肺病入院）重度恶化的风险比和95%置信区间。还评估了这些药物是否与中度恶化（定义为口服皮质类固醇和抗生素的联合处方以及同一天门诊诊断为急性慢性阻塞性肺疾病加重）的风险降低有关。

与磺酰脲类药物相比，GLP-1受体激动剂可降低30%的重度恶化风险（分别为3.5与5.0事件/100人-年；危险比为0.70）和中度恶化风险（0.63）。DPP-4抑制剂与重度恶化（分别为4.6与5.1事件/100人-年；危险比为0.91）和中度恶化（0.93）的发生率略微降低有关，置信区间包括零值。最后，SGLT-2抑制剂可降低38%的重度恶化风险（分别为2.4与3.9事件/100人-年；危险比为0.62），但不可降低中度恶化风险（1.02）。

研究结果表明，在这项以人群为基础的研究中，与磺酰脲类药物相比，GLP-1受体激动剂和SGLT-2抑制剂与慢性阻塞性肺病和2型糖尿病患者病情严重恶化的风险降低相关。DPP-4抑制剂与慢性阻塞性肺疾病恶化风险的降低没有明显关联。

附：英文原文

Title: Novel antihyperglycaemic drugs and prevention of chronic obstructive pulmonary disease exacerbations among patients with type 2 diabetes: population based cohort study

Author: Richeek Pradhan, Sally Lu, Hui Yin, Oriana H Y Yu, Pierre Ernst, Samy Suissa, Laurent Azoulay

Issue&Volume: 2022/11/01

Abstract:

Objective To determine whether the use of glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, separately, is associated with a decreased risk of exacerbations of chronic obstructive pulmonary disease among patients with chronic obstructive pulmonary disease and type 2 diabetes.

Design Population based cohort study using an active comparator, new user design.

Setting The United Kingdom Clinical Practice Research Datalink linked with the Hospital Episode Statistics Admitted Patient Care and Office for National Statistics databases.

Participants Three active comparator, new user cohorts of patients starting the study drugs (GLP-1 receptor agonists, DPP-4 inhibitors, or SGLT-2 inhibitors) or sulfonylureas with a history of chronic obstructive pulmonary disease. The first cohort included 1252 patients starting GLP-1 receptor agonists and 14259 starting sulfonylureas, the second cohort included 8731 patients starting DPP-4 inhibitors and 18204 starting sulfonylureas, and the third cohort included 2956 patients starting SGLT-2 inhibitors and 10841 starting sulfonylureas.

Main outcome measures Cox proportional hazards models with propensity score fine stratification weighting were fitted to estimate hazard ratios and 95% confidence intervals of severe exacerbation of chronic obstructive pulmonary disease (defined as hospital admission for chronic obstructive pulmonary disease), separately for GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors. Whether these drugs were associated with a decreased risk of moderate exacerbation (defined as a co-prescription of an oral corticosteroid and an antibiotic along with an outpatient diagnosis of acute chronic obstructive pulmonary disease exacerbation on the same day) was also assessed.

Results Compared with sulfonylureas, GLP-1 receptor agonists were associated with a 30% decreased risk of severe exacerbation (3.5 v 5.0 events per 100 person years; hazard ratio 0.70, 95% confidence interval 0.49 to 0.99) and moderate exacerbation (0.63, 0.43 to 0.94). DPP-4 inhibitors were associated with a modestly decreased incidence of severe exacerbation (4.6 v. 5.1 events per 100 person years; hazard ratio 0.91, 0.82 to 1.02) and moderate exacerbation (0.93, 0.82 to 1.07), with confidence intervals including the null value. Finally, SGLT-2 inhibitors were associated with a 38% decreased risk of severe exacerbation (2.4 v 3.9 events per 100 person years; hazard ratio 0.62, 0.48 to 0.81) but not moderate exacerbation (1.02, 0.83 to 1.27).

Conclusions In this population based study, GLP-1 receptor agonists and SGLT-2 inhibitors were associated with a reduced risk of severe exacerbations compared with sulfonylureas in patients with chronic obstructive pulmonary disease and type 2 diabetes. DPP-4 inhibitors were not clearly associated with a decreased risk of chronic obstructive pulmonary disease exacerbations.

DOI: 10.1136/bmj-2022-071380

Source: https://www.bmj.com/content/379/bmj-2022-071380