Celsa Ciro, Pennisi Grazia, Tulone Adele, Ciancimino Giacinta, Vaccaro Marco, Infantino Giuseppe, Di Maria Gabriele, Pinato David J, Cabibbo Giuseppe, Enea Marco, Mantovani Alessandro, Tilg Herbert, Targher Giovanni, Cammà Calogero, Petta Salvatore
Gastroenterology and Hepatology Unit, Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, University of Palermo, Palermo, Italy.
Department of Surgery & Cancer, Imperial College London, London, UK.
Gut. 2025 Apr 7;74(5):815-824. doi: 10.1136/gutjnl-2024-334591.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising effects on liver histology in phase 2 trials enrolling patients with metabolic dysfunction-associated steatotic liver disease. However, the impact of GLP-1RAs on the long-term risk of major adverse liver-related outcomes (MALOs) remains uncertain.
We performed a meta-analysis of observational cohort studies to quantify the magnitude and direction of the association between GLP-1RA use and MALOs in people with type 2 diabetes (T2D).
We systematically searched eligible cohort studies comparing GLP-1RA new users versus users of other glucose-lowering medications. The primary outcome was the cumulative incidence rates of MALOs. Secondary outcomes included hepatic decompensation events, hepatocellular carcinoma (HCC) and liver-related mortality. Random-effects models were used to calculate incidence rate ratios (IRRs).
11 retrospective cohort studies with aggregate data on 1 467 220 patients with T2D (647 903 GLP-1RA new users, 819 317 non-users) were included. GLP-1RA use was significantly associated with a lower risk of MALOs (IRR 0.71, 95% CI 0.57 to 0.88) and hepatic decompensation (IRR 0.70, 95% CI 0.52 to 0.94). Association with reduced risk of HCC was also observed (IRR 0.82, 95% CI 0.61 to 1.11). Compared with other antidiabetic medications, GLP-1RAs showed superior effectiveness versus SGLT2 inhibitors in preventing MALOs (IRR 0.93, 95% CI 0.87 to 0.99), versus DPP-4 inhibitors in preventing hepatic decompensation (IRR 0.74, 95% CI 0.66 to 0.83) and versus insulin therapy in preventing HCC (IRR 0.32, 95% CI 0.13 to 0.80).
GLP-1RA use is associated with a lower risk of liver-related complications and hepatic decompensation in people with T2D. These findings suggest a role of GLP-1RAs in preventing liver-related complications beyond their beneficial cardiometabolic effects.
在纳入代谢功能障碍相关脂肪性肝病患者的2期试验中，胰高血糖素样肽-1受体激动剂（GLP-1RAs）已显示出对肝脏组织学有良好效果。然而，GLP-1RAs对主要肝脏相关不良结局（MALOs）长期风险的影响仍不确定。
我们对观察性队列研究进行了荟萃分析，以量化2型糖尿病（T2D）患者使用GLP-1RA与MALOs之间关联的程度和方向。
我们系统检索了比较GLP-1RA新使用者与其他降糖药物使用者的合格队列研究。主要结局是MALOs的累积发病率。次要结局包括肝失代偿事件、肝细胞癌（HCC）和肝脏相关死亡率。采用随机效应模型计算发病率比（IRRs）。
纳入了11项回顾性队列研究，汇总数据涉及1467220例T2D患者（647903例GLP-1RA新使用者，819317例非使用者）。使用GLP-1RA与较低的MALOs风险（IRR 0.71，95%CI 0.57至0.88）和肝失代偿风险（IRR 0.70，95%CI 0.52至0.94）显著相关。还观察到与降低HCC风险有关（IRR 0.82，95%CI 0.61至1.11）。与其他抗糖尿病药物相比，GLP-1RAs在预防MALOs方面优于钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂（IRR 0.93，95%CI 0.87至0.99），在预防肝失代偿方面优于二肽基肽酶-4（DPP-4）抑制剂（IRR 0.74，95%CI 0.66至0.83），在预防HCC方面优于胰岛素治疗（IRR 0.32，95%CI 0.13至0.80）。
T2D患者使用GLP-1RA与较低的肝脏相关并发症和肝失代偿风险相关。这些发现表明GLP-1RAs在预防肝脏相关并发症方面发挥作用，超出了其有益的心脏代谢效应。
