Rashid Zayed, Woldesenbet Selamawit, Khalil Mujtaba, Iyer Sidharth, Khan Muhammad Muntazir Mehdi, Altaf Abdullah, Munir Muhammad Musaab, Catalano Giovanni, Mumtaz Khalid, Pawlik Timothy M
Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio, USA.
Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, College of Medicine, The Ohio State University, Columbus, Ohio, USA.
Liver Int. 2025 Apr;45(4):e16132. doi: 10.1111/liv.16132. Epub 2024 Oct 15.
We sought to characterise the impact of GLP-1RA on adverse liver outcomes (ALO) among patients with alcohol-associated liver disease (ALD) and Type 2 diabetes mellitus (T2DM).
Patients with T2DM newly diagnosed with ALD between 2013 and 2020 were identified using IBM MarketScan database and were categorised by GLP-1RA exposure. Overlap propensity score weighting (OPSW) followed by Poisson regression models was used to analyse adjusted risk of ALO, a composite endpoint defined by first occurrence of hepatic decompensation (HD), portal hypertension (PH), hepatocellular carcinoma (HCC) or liver transplantation (LT) relative to GLP-1RA.
Among 14 730 patients, most individuals were male (n = 9752, 66.2%) with median age of 57 (IQR 52-61) years; 2.2% (n = 317) of patients had GLP-1RA exposure. Overall, 32.0% (n = 4717) of patients experienced HD, 15.9% (n = 2345) had PH, 3.8% (n = 563) developed HCC, while 2.5% (n = 374) underwent transplantation. Non-GLP-1RA patients had higher incidence of HD (32.2% vs. 22.4%) and HCC (3.9% vs. 0.3%) versus patients taking GLP-1RA (both p < 0.001); in contrast, there was no difference in incidence of PH (14.5% vs. 16.0%) and LT (1.3% vs. 2.6%) (both p > 0.05). After OPSW, overall incidence of ALO was lower in GLP-1RA cohort (GLP-1RA: 12.0%, 95%CI 9.0-16.0 vs. non-GLP-1RA: 21.0%, 95%CI 20.0-22.0) with an absolute incidence risk reduction of 9.0% (95%CI 3.0%-15.0%) associated with GLP-1RA. GLP-1RA was most strongly associated with lower likelihood of HD with reduced adjusted incidence rate of 0.56 (95%CI 0.36-0.86) relative to non-GLP-1RA individuals.
GLP-1RA may have a hepatoprotective impact among patients with ALD and T2DM.
我们试图明确胰高血糖素样肽-1受体激动剂（GLP-1RA）对酒精性肝病（ALD）合并2型糖尿病（T2DM）患者不良肝脏结局（ALO）的影响。
利用IBM MarketScan数据库识别出2013年至2020年间新诊断为ALD的T2DM患者，并根据GLP-1RA暴露情况进行分类。采用重叠倾向评分加权（OPSW），随后进行泊松回归模型分析，以评估ALO的调整后风险，ALO是一个复合终点，定义为首次出现肝失代偿（HD）、门静脉高压（PH）、肝细胞癌（HCC）或肝移植（LT）相对于GLP-1RA的情况。
在14730例患者中，大多数为男性（n = 9752，66.2%），中位年龄为57岁（四分位间距52 - 61岁）；2.2%（n = 317）的患者有GLP-1RA暴露。总体而言，32.0%（n = 4717）的患者经历了HD，15.9%（n = 2345）有PH，3.8%（n = 563）发生了HCC，而2.5%（n = 374）接受了移植。与服用GLP-1RA的患者相比，未使用GLP-1RA的患者HD（32.2%对22.4%）和HCC（3.9%对0.3%）的发生率更高（均p < 0.001）；相比之下，PH（14.5%对16.0%）和LT（1.3%对2.6%）的发生率没有差异（均p > 0.05）。经过OPSW后，GLP-1RA队列中ALO的总体发生率较低（GLP-1RA：12.0%，95%CI 9.0 - 16.0对未使用GLP-1RA：21.0%，95%CI 20.0 - 22.0），与GLP-1RA相关的绝对发生率风险降低了9.0%（95%CI 3.0% - 15.0%）。GLP-1RA与HD可能性降低的关联最为强烈，相对于未使用GLP-1RA的个体，调整后的发生率降低了0.56（95%CI 0.36 - 0.86）。
GLP-1RA可能对ALD合并T2DM患者具有肝脏保护作用。
