钠-葡萄糖协同转运蛋白2抑制剂与代谢功能障碍相关脂肪性肝病的心血管结局：一项真实世界回顾性队列研究

SGLT2 Inhibitors and Cardiovascular Outcomes in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Real-World Retrospective Cohort Study.

作者信息

Pham Hoang Nhat, Ibrahim Ramzi, Mouhaffel Rama, Abdelnabi Mahmoud, Ozturk Nazli Begum, Elshaer Amany, Habib Eiad, Farina Juan, Ayoub Chadi, Lee Justin Z, Chahal Anwar, Lee Kwan, Arsanjani Reza, Singh Amitoj

机构信息

Department of Medicine, University of Arizona-Tucson, United States; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minn, United States.

Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, Ariz, United States.

出版信息

Am J Med. 2025 Jun 24. doi: 10.1016/j.amjmed.2025.06.039.

DOI:10.1016/j.amjmed.2025.06.039

PMID:40571041

Abstract

INTRODUCTION

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent global health issue associated with increased cardiovascular risk. SGLT2 inhibitors offer cardioprotective benefits and may improve MASLD-related outcomes. We aimed to investigate the association between SGLT2 inhibitors use and cardio-hepatic events in patients with MASLD.

METHODS

We conducted a retrospective cohort study using the TriNetX Network, including 1,280,057 adults (≥18 years) with MASLD without prior alcohol-associated liver disease between 2014 and 2022. Patients were stratified by SGLT2 inhibitors use. Propensity score matching (1:1, PSM) was performed to balance baseline characteristics between two cohorts. Hazard ratio (HR) with 95% confidence intervals (CIs) were calculated using Cox proportional hazard models.

RESULTS

After PSM, there were 69,970 patients with MASLD per each cohort. Mean follow-up was 3.70±2.08 and 4.14±2.66 years for SGLT2 inhibitor users and non-users, respectively. SGLT2 inhibitor use was associated with lower all-cause mortality (HR 0.600 [95% CI, 0.580-0.621]) and hospitalization (HR 0.788 [0.777-0.800]). Cardiovascular benefits included reduced risks of acute heart failure exacerbation (HR 0.872 [0.849-0.896]), acute myocardial infarction (HR 0.916 [0.882-0.952]), cerebral infarction (HR 0.954 [0.916-0.994]), and cardiac arrest (HR 0.661 [0.609-0.718]). Hepatic outcomes showed lower risks of acute liver failure (HR 0.704 [0.643-0.770]) and cirrhosis (HR 0.898 [0.861-0.936]). Safety analysis revealed a lower incidence of acute kidney injury (HR 0.797 [0.779-0.816]) without significant difference for hypoglycemia (HR 0.963 [0.914-1.014]).

CONCLUSIONS

SGLT2 inhibitors in MASLD patients were associated with reduced mortality, hospitalization, cardiovascular events, and liver complications, highlighting potential benefits beyond glycemic control.

摘要

引言

代谢功能障碍相关脂肪性肝病（MASLD）是一个普遍的全球健康问题，与心血管风险增加相关。钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂具有心脏保护作用，可能改善与MASLD相关的结局。我们旨在研究SGLT2抑制剂的使用与MASLD患者的心肝事件之间的关联。

方法

我们使用TriNetX网络进行了一项回顾性队列研究，纳入了2014年至2022年间1,280,057名年龄≥18岁、患有MASLD且无既往酒精性肝病的成年人。患者根据是否使用SGLT2抑制剂进行分层。进行倾向评分匹配（1:1，PSM）以平衡两个队列之间的基线特征。使用Cox比例风险模型计算95%置信区间（CI）的风险比（HR）。

结果

PSM后，每个队列有69,970名MASLD患者。SGLT2抑制剂使用者和非使用者的平均随访时间分别为3.70±2.08年和4.14±2.66年。使用SGLT2抑制剂与较低的全因死亡率（HR 0.600 [95% CI，0.580 - 0.621]）和住院率（HR 0.788 [0.777 - 0.800]）相关。心血管益处包括急性心力衰竭加重风险降低（HR 0.872 [0.849 - 0.896]）、急性心肌梗死（HR 0.916 [0.882 - 0.952]）、脑梗死（HR 0.954 [0.916 - 0.994]）和心脏骤停（HR 0.661 [0.609 - 0.718]）。肝脏结局显示急性肝衰竭风险降低（HR 0.704 [0.643 - 0.770]）和肝硬化风险降低（HR 0.898 [0.861 - 0.936]）。安全性分析显示急性肾损伤发生率较低（HR 0.797 [0.779 - 0.816]），低血糖发生率无显著差异（HR 0.963 [0.914 - 1.014]）。