Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis: A Narrative Review

Glucagon-like peptide-1 (GLP-1), an incretin hormone, plays a crucial role in glucose homeostasis by stimulating insulin secretion, suppressing glucagon release, and delaying gastric emptying. Its therapeutic potential was long realized, leading to the development of the first GLP-1 receptor agonist, exenatide, followed by liraglutide, dulaglutide, semaglutide, and tirzepatide. Semaglutide is available as a weekly subcutaneous injection with high bioavailability. Semaglutide is the only GLP-1 agonist available for oral therapy, used in the treatment of type 2 diabetes mellitus (T2DM). Semaglutide has demonstrated broad clinical efficacy beyond glycemic control, including weight reduction, cardiovascular risk reduction, and, most recently, in the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Semaglutide therapy is associated with the resolution of steatohepatitis and improvement in hepatic fibrosis in patients with MASH. Alongside resmetirom, semaglutide is currently approved for the treatment of non-cirrhotic MASH with moderate-to-advanced fibrosis. Safety considerations include gastrointestinal intolerance, hypoglycemia, rare pancreaticobiliary events, and theoretical concerns of thyroid C-cell tumors, though human risk remains minimal. In summary, semaglutide extends the armamentarium of the hepatologist against the most common liver disease worldwide.