Kuo Chia-Chih, Li Chun-Hsien, Chuang Min-Hsiang, Huang Po-Yu, Kuo Hsing-Tao, Lai Chih-Cheng
Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan.
Department of Physical Medicine and Rehabilitation, Chi Mei Medical Center, Tainan, Taiwan.
Aliment Pharmacol Ther. 2025 Apr;61(8):1343-1356. doi: 10.1111/apt.70007. Epub 2025 Jan 31.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in reducing alcohol consumption, but their impact on clinical outcomes in patients with alcohol use disorder (AUD) remains unclear. We investigated the association between GLP-1RAs and the development and progression of alcohol-related liver disease (ArLD) in patients with AUD.
Using the TriNetX Research Network, we conducted two retrospective cohort studies comparing GLP-1RAs versus dipeptidyl peptidase-4 inhibitors (DPP-4is) in patients with type 2 diabetes. The first cohort included patients with AUD but without ArLD (n = 7132 after propensity score matching), while the second comprised patients with established ArLD (n = 1896 after matching). Primary outcomes were incident ArLD in the AUD cohort and hepatic decompensation in the ArLD cohort.
In the AUD cohort (median follow-up: 63.2 months), GLP-1RA users showed significantly lower risks of developing ArLD compared to DPP-4i users (incidence rate: 6.0 vs. 8.7 per 1000 person-years; HR: 0.62, 95% CI: 0.44-0.87, p = 0.006). GLP-1RAs were also associated with reduced risks of all-cause mortality (HR: 0.53, p < 0.001). In the ArLD cohort (median follow-up: 28.2 months), GLP-1RA users demonstrated lower risks of hepatic decompensation (incidence rate: 39.5 vs. 51.4 per 1000 person-years; HR: 0.66, 95% CI: 0.51-0.85, p = 0.001) and all-cause mortality (HR: 0.53, p < 0.001) compared to DPP-4i users.
GLP-1RAs were associated with reduced risks of developing and progressing ArLD in patients with AUD, suggesting potential therapeutic benefits in this population.
胰高血糖素样肽-1受体激动剂（GLP-1RAs）在减少酒精摄入方面显示出前景，但其对酒精使用障碍（AUD）患者临床结局的影响仍不明确。我们调查了GLP-1RAs与AUD患者酒精性肝病（ArLD）的发生和进展之间的关联。
利用TriNetX研究网络，我们进行了两项回顾性队列研究，比较2型糖尿病患者中GLP-1RAs与二肽基肽酶-4抑制剂（DPP-4is）的疗效。第一个队列包括患有AUD但无ArLD的患者（倾向评分匹配后n = 7132），而第二个队列包括已确诊ArLD的患者（匹配后n = 1896）。主要结局是AUD队列中的ArLD发病情况以及ArLD队列中的肝失代偿情况。
在AUD队列（中位随访时间：63.2个月）中，与DPP-4i使用者相比，GLP-1RA使用者发生ArLD的风险显著更低（发病率：每1000人年6.0例 vs. 8.7例；HR：0.62，95%CI：0.44 - 0.87，p = 0.006）。GLP-1RAs还与全因死亡率降低相关（HR：0.53，p < 0.001）。在ArLD队列（中位随访时间：28.2个月）中，与DPP-4i使用者相比，GLP-1RA使用者肝失代偿风险更低（发病率：每1000人年39.5例 vs. 51.4例；HR：0.66，95%CI：0.51 - 0.85，p = 0.001），全因死亡率也更低（HR：0.53，p < 0.001）。
GLP-1RAs与AUD患者发生和进展ArLD的风险降低相关，提示对该人群具有潜在的治疗益处。
