胰高血糖素样肽-1受体激动剂与2型糖尿病合并代谢功能障碍相关肝病患者生存率提高及肝脏相关事件减少相关：一项大型真实世界回顾性研究
Glucagon-like Peptide-1 Receptor Agonists Are Associated With Improved Survival and Reduced Liver-Related Events in Patients With Type 2 Diabetes and Metabolic Dysfunction-Associated Liver Disease: A Large Real-World Retrospective Study.
作者信息
Liu Benjamin D, Aly Mohammed, Hsin-Ti Lin Cindy, Panesar Noordeep, Hill Hannah, Qureshi Kamran
机构信息
Department of Medicine, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio.
Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
出版信息
Endocr Pract. 2025 Apr 28. doi: 10.1016/j.eprac.2025.04.017.
OBJECTIVES
To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or pioglitazone (PGZ) are associated with improved survival, reduced liver-related outcomes (LROs), and better metabolic outcomes in patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated liver disease (MASLD) or steatohepatitis (MASH).
METHODS
We used the TriNetX platform to identify adults with T2DM and MASLD/MASH from 2006 onward (n = 558 075) using Internation Classification of Diseases codes. Patients with confounding liver diseases, overlapping study medications, or bariatric surgery were excluded. Three exclusive cohorts-GLP-1 RA, PGZ, and other antidiabetic agents (controls)-were formed. After 1:1 propensity score matching, time-to-event analyses were performed using Cox proportional hazards models and Kaplan-Meier methods.
RESULTS
Among matched groups, GLP-1 RAs (n = 17 465) were associated with a 40.9% reduction in all-cause mortality versus controls (hazard ratio [HR] 0.59; P < .0001) and significantly lower rates of LRO (HR 0.77) and liver transplantation (HR 0.33). In contrast, PGZ (n = 1803) showed reduced LRO rates (HR 0.68) but not mortality. In cirrhotic patients, GLP-1 RA was linked to fewer transplant events but did not significantly reduce mortality. GLP-1 RA therapy noted greater reductions in body mass index and hemoglobin A1c relative to controls.
CONCLUSIONS
In this large real-world cohort, GLP-1 RA use was associated with improved survival and hepatic outcomes in T2DM patients with MASLD/MASH, particularly among those without established cirrhosis. PGZ exhibited hepatic benefits. These findings highlight the potential importance of further prospective studies to evaluate early GLP-1 RA therapy in this high-risk diabetic population with MASLD/MASH.
目的
评估胰高血糖素样肽-1受体激动剂（GLP-1 RAs）或吡格列酮（PGZ）是否与2型糖尿病（T2DM）合并代谢功能障碍相关肝病（MASLD）或脂肪性肝炎（MASH）患者的生存率提高、肝脏相关结局（LROs）降低及更好的代谢结局相关。
方法
我们使用TriNetX平台，根据国际疾病分类编码，从2006年起识别患有T2DM和MASLD/MASH的成年人（n = 558075）。排除患有混杂性肝病、重叠研究用药或接受减重手术的患者。形成了三个独立队列——GLP-1 RA、PGZ和其他抗糖尿病药物（对照组）。在1:1倾向评分匹配后，使用Cox比例风险模型和Kaplan-Meier方法进行事件发生时间分析。
结果
在匹配组中，与对照组相比，GLP-1 RAs（n = 17465）使全因死亡率降低40.9%（风险比[HR] 0.59；P <.0001），LRO发生率（HR 0.77）和肝移植率（HR 0.33）显著更低。相比之下，PGZ（n = 1803）显示LRO发生率降低（HR 0.68），但未降低死亡率。在肝硬化患者中，GLP-1 RA与较少的移植事件相关，但未显著降低死亡率。与对照组相比，GLP-1 RA治疗使体重指数和糖化血红蛋白降低幅度更大。
结论
在这个大型真实世界队列中，使用GLP-1 RA与T2DM合并MASLD/MASH患者的生存率提高和肝脏结局改善相关，尤其是在那些未发生肝硬化的患者中。PGZ显示出肝脏益处。这些发现凸显了进一步开展前瞻性研究以评估在这个患有MASLD/MASH的高危糖尿病患者群体中早期使用GLP-1 RA治疗的潜在重要性。
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