SGLT2抑制剂在代谢功能障碍相关脂肪性肝病（MASLD）中除了具有心脏代谢益处外，还具有持续的肝脏益处。

SGLT2 Inhibitors in MASLD (Metabolic Dysfunction-Associated Steatotic Liver Disease) Associated with Sustained Hepatic Benefits, Besides the Cardiometabolic.

作者信息

Suki Mohamad, Imam Ashraf, Amer Johnny, Milgrom Yael, Massarwa Muhammad, Hazou Wadi, Tiram Yariv, Perzon Ofer, Sharif Yousra, Sackran Joseph, Alon Revital, Lourie Nachum, Hershko Klement Anat, Shibli Safa, Safadi Tamer, Raz Itamar, Khalaileh Abed, Safadi Rifaat

机构信息

Institution of Liver Diseases, Hadassah Medical Organization, Hadassah-Hebrew University, Jerusalem 91120, Israel.

Transplantation Unit, Department of Surgery, Hadassah Medical Organization, Hadassah-Hebrew University, Jerusalem 91120, Israel.

出版信息

Pharmaceuticals (Basel). 2025 Jul 26;18(8):1118. doi: 10.3390/ph18081118.

DOI:10.3390/ph18081118

PMID:40872510

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12389333/

Abstract

: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown promise in metabolic dysfunction-associated steatotic liver disease (MASLD). This large real-world study aimed to evaluate the effects of SGLT2 inhibitors on MASLD patients' clinical outcomes and liver-related complications over extended follow-up. : Data were sourced from TriNetX, a global health research platform with de-identified electronic medical records spanning 135 million patients across 112 healthcare organizations worldwide. We included MASLD adults diagnosed according to ICD9/10 criteria. Following propensity score matching based on 34 variables (demographics, comorbidities, laboratory tests and medication history), SGLT2 inhibitor-treated (n = 19,922) patients were compared with non-SGLT2 inhibitor (n = 19,922) cases. Exclusion criteria included baseline improved alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels > 4 upper normal limit (UNL), baseline advanced liver disease, liver transplant and cancer, past anticoagulation and non-MASLD etiologies. Assessed outcomes included survival, biochemical, hematologic, AFP, metabolic and cardiovascular parameters, progression to advanced liver disease (ALD), synthetic function, and metabolic markers over 1, 5, and 10 years. : Following matching, both cohorts were well-balanced across baseline characteristics. After one year, the SGLT2 inhibitor group demonstrated significantly reduced BMI (33.2 ± 6.2 vs. 34.1 ± 6.5 kg/m, < 0.001), improved ALT (40.3 ± 31.5 vs. 48.3 ± 41.2 U/L, < 0.001), and better glycemic control (HbA1c 7.35 ± 1.51% vs. 7.93 ± 1.72%, < 0.001). The SGLT2 inhibitor group showed higher 10-year survival rates (95.00% vs. 88.69%, < 0.001), fewer cardiovascular events (10.19% vs. 11.80%, < 0.001), and markedly reduced progression to advanced liver disease (6.90% vs. 14.15%, < 0.001). These benefits were consistent across clinical, laboratory, and medication-defined ALD categories. Notably, rates of hepatic decompensation events were significantly lower with SGLT2 inhibitor therapy. : In this large real-world cohort, SGLT2 inhibitor use in MASLD patients was associated with significantly improved long-term survival, cardiovascular, and liver-related outcomes over 10 years of follow-up. These benefits likely result from combined metabolic improvements, anti-inflammatory effects, and direct hepatoprotective mechanisms. SGLT2 inhibitors represent a promising therapeutic strategy for improving outcomes in MASLD.

摘要

钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂已在代谢功能障碍相关脂肪性肝病（MASLD）中展现出前景。这项大型真实世界研究旨在评估SGLT2抑制剂在长期随访中对MASLD患者临床结局及肝脏相关并发症的影响。

数据来源于TriNetX，这是一个全球健康研究平台，拥有来自全球112个医疗机构的1.35亿例患者的去识别电子病历。我们纳入了根据ICD9/10标准诊断的成年MASLD患者。基于34个变量（人口统计学、合并症、实验室检查和用药史）进行倾向得分匹配后，将接受SGLT2抑制剂治疗的患者（n = 19922）与未使用SGLT2抑制剂的患者（n = 19922）进行比较。排除标准包括基线时丙氨酸氨基转移酶（ALT）和碱性磷酸酶（ALP）水平改善且高于正常上限（UNL）的4倍、基线时晚期肝病、肝移植和癌症、既往抗凝治疗以及非MASLD病因。评估的结局包括1年、5年和10年的生存率、生化指标、血液学指标、甲胎蛋白（AFP）、代谢指标和心血管参数、进展为晚期肝病（ALD）、合成功能以及代谢标志物。

匹配后，两个队列在基线特征方面均衡良好。1年后，SGLT2抑制剂组的体重指数（BMI）显著降低（33.2±6.2 vs. 34.1±6.5 kg/m²，P < 0.001），ALT改善（40.3±31.5 vs. 48.3±41.2 U/L，P < 0.001），血糖控制更好（糖化血红蛋白[HbA1c] 7.35±1.51% vs. 7.93±1.72%，P < 0.001）。SGLT2抑制剂组的10年生存率更高（95.00% vs. 88.69%，P < 0.001），心血管事件更少（10.19% vs. 11.80%，P < 0.001），进展为晚期肝病的情况明显减少（6.90% vs. 14.15%，P < 0.001）。这些益处贯穿临床、实验室和药物定义的ALD类别。值得注意的是，SGLT2抑制剂治疗的肝失代偿事件发生率显著更低。

在这个大型真实世界队列中，MASLD患者使用SGLT2抑制剂与随访10年期间显著改善的长期生存、心血管及肝脏相关结局相关。这些益处可能源于代谢改善、抗炎作用和直接肝脏保护机制的综合作用。SGLT2抑制剂是改善MASLD结局的一种有前景的治疗策略。