加拿大犹太总医院Kristian B Filion团队评估了钠葡萄糖协同转运蛋白2抑制剂治疗与重大不良心血管事件风险的相关性。该成果于2020年9月23日发表在《英国医学杂志》上。

为了在临床实践中比较钠葡萄糖协同转运蛋白2（SGLT2）抑制剂和二肽基肽酶-4（DPP-4）抑制剂治疗2型糖尿病患者发生心血管事件的风险，研究组使用2013-2018年加拿大七个省和英国的行政医疗数据库，使用新用户设计和随后的荟萃分析进行了一项多数据库回顾性队列研究。

研究组共纳入使用SGLT2抑制剂的209867名新参与者，与使用DPP-4抑制剂的209867名参与者，平均随访0.9年。主要结局是重大不良心血管事件（MACE，包括心肌梗死、缺血性中风或心血管死亡的综合结局）。

与DPP-4抑制剂相比，SGLT2抑制剂显著降低了MACE（每1000人年的发生率分别为11.4例和16.5例，风险比为0.76）、心肌梗死（5.1例和6.4例，0.82）、心血管死亡（3.9例和7.7例，0.60）、心力衰竭（3.1例和7.7例，0.43）和全因死亡（8.7例和17.3例，0.60）的风险。SGLT2抑制剂对缺血性卒中轻微获益（2.6例和3.5例，0.85）。使用卡格列净（0.79）、达格列净（0.73）和恩格列净（0.77）治疗均可降低MACE风险。

研究结果表明，与使用DPP-4抑制剂相比，短期使用SGLT2抑制剂可显著降低心血管事件的风险。

附：英文原文

Title: Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study

Author: Kristian B Filion, Lisa M Lix, Oriana HY Yu, Sophie Dell’Aniello, Antonios Douros, Baiju R Shah, Audray St-Jean, Anat Fisher, Eric Tremblay, Shawn C Bugden, Silvia Alessi-Severini, Paul E Ronksley, Nianping Hu, Colin R Dormuth, Pierre Ernst, Samy Suissa

Issue&Volume: 2020/09/23

Abstract:

Objective To compare the risk of cardiovascular events between sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors among people with type 2 diabetes in a real world context of clinical practice.

Design Multi-database retrospective cohort study using a prevalent new user design with subsequent meta-analysis.

Setting Canadian Network for Observational Drug Effect Studies (CNODES), with administrative healthcare databases from seven Canadian provinces and the United Kingdom, 2013-18.

Population 209867 new users of a SGLT2 inhibitor matched to 209867 users of a DPP-4 inhibitor on time conditional propensity score and followed for a mean of 0.9 years.

Main outcome measures The primary outcome was major adverse cardiovascular events (MACE, a composite of myocardial infarction, ischaemic stroke, or cardiovascular death). Secondary outcomes were the individual components of MACE, heart failure, and all cause mortality. Cox proportional hazards models were used to estimate site specific adjusted hazards ratios and 95% confidence intervals, comparing use of SGLT2 inhibitors with use of DPP-4 inhibitors in an as treated approach. Site specific results were pooled using random effects meta-analysis.

Results Compared with DPP-4 inhibitors, SGLT2 inhibitors were associated with decreased risks of MACE (incidence rate per 1000 person years: 11.4 v 16.5; hazard ratio 0.76, 95% confidence interval 0.69 to 0.84), myocardial infarction (5.1 v 6.4; 0.82, 0.70 to 0.96), cardiovascular death (3.9 v 7.7; 0.60, 0.54 to 0.67), heart failure (3.1 v 7.7; 0.43, 0.37 to 0.51), and all cause mortality (8.7 v 17.3; 0.60, 0.54 to 0.67). SGLT2 inhibitors had more modest benefits for ischaemic stroke (2.6 v 3.5; 0.85, 0.72 to 1.01). Similar benefits for MACE were observed with canagliflozin (0.79, 0.66 to 0.94), dapagliflozin (0.73, 0.63 to 0.85), and empagliflozin (0.77, 0.68 to 0.87).

Conclusions In this large observational study conducted in a real world clinical practice context, the short term use of SGLT2 inhibitors was associated with a decreased risk of cardiovascular events compared with the use of DPP-4 inhibitors.

DOI: 10.1136/bmj.m3342

Source: https://www.bmj.com/content/370/bmj.m3342