Petrie Gavin N, Mayo Leah M
Department of Psychiatry.
Mathison Centre for Mental Health Education and Research, and.
J Clin Invest. 2025 May 1;135(9). doi: 10.1172/JCI192414.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs), such as semaglutide, are widely used in the treatment of metabolic disorders, including type 2 diabetes (T2D) and obesity. These medications primarily function by enhancing insulin secretion; however, emerging evidence suggests that the effects extend beyond metabolic regulation. In this issue of the JCI, Farokhnia et al. evaluated the effects of GLP-1RAs alongside another T2D treatment, dipeptidyl peptidase-4 inhibitors (DPP-4Is), on alcohol consumption in humans and preclinical models. In humans, GLP1-RAs, but not DPP-4Is, were associated with reductions in alcohol consumption. Similarly, DPP-4 inhibition had no effect on alcohol intake in rodents. These findings invite further exploration of the mechanisms by which GLP-1RAs reduce alcohol consumption and redefine our pharmacotherapy approach to alcohol use disorder (AUD) by opening the possibility for application as an early harm-reduction tool.
胰高血糖素样肽-1受体激动剂（GLP-1RAs），如司美格鲁肽，被广泛用于治疗代谢紊乱，包括2型糖尿病（T2D）和肥胖症。这些药物主要通过增强胰岛素分泌发挥作用；然而，新出现的证据表明，其作用超出了代谢调节范围。在本期《临床研究杂志》中，法罗赫尼亚等人评估了GLP-1RAs与另一种T2D治疗药物二肽基肽酶-4抑制剂（DPP-4Is）对人类和临床前模型酒精摄入量的影响。在人类中，GLP-1RAs而非DPP-4Is与酒精摄入量减少有关。同样，DPP-4抑制对啮齿动物的酒精摄入量没有影响。这些发现促使人们进一步探索GLP-1RAs减少酒精摄入的机制，并通过开辟将其作为早期减少伤害工具应用的可能性，重新定义我们对酒精使用障碍（AUD）的药物治疗方法。
