Semaglutide demonstrates potential to mitigate drug-induced liver injury via anti-inflammatory and antioxidant actions

Drug-induced liver injury (DILI) is a significant clinical challenge, stemming from medications, illicit drugs, or supplements, and is characterized by inflammation, oxidative stress, and mitochondrial dysfunction. Current therapeutic options for DILI are limited, driving the urgent need for novel hepatoprotective agents. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is primarily known for its antidiabetic and anti-obesity effects, but also exerts pleiotropic actions through GLP-1R activation. Its recent approval for metabolic dysfunction-associated steatohepatitis highlights its liver-beneficial potential.

This perspective piece synthesizes existing preclinical evidence and proposed mechanisms for semaglutide's hepatoprotective effects against drug-induced liver injury (DILI). It examines how GLP-1R activation influences key pathological processes such as inflammation, oxidative stress, and mitochondrial dysfunction in the context of liver damage. The review draws upon findings from various preclinical models of toxic and ischemic liver injury to evaluate the therapeutic potential of GLP-1 RAs.

Preclinical studies in models of toxic and ischemic liver injury consistently demonstrate that GLP-1 RAs, including semaglutide, effectively reduce hepatic damage. The proposed mechanisms underlying semaglutide's liver-beneficial effects are multifaceted, encompassing anti-inflammatory, antioxidant, and anti-apoptotic actions. Furthermore, semaglutide is thought to improve hepatic microcirculation, reduce lipotoxicity, and enhance the liver's regenerative capacity. These pleiotropic effects, mediated by GLP-1R activation, position semaglutide as a promising candidate for DILI treatment. > Semaglutide may offer therapeutic benefits in DILI, either as supportive treatment or as a stabilizing agent prior to liver transplantation, by targeting inflammation, oxidative stress, and cellular damage pathways.