Via practica 2/2026

Incretin agonists in the treatment of MASLD and MASH: A comparison of three therapeutic approaches

Metabolically associated steatohepatitis (MASLD) and its progression to metabolically associated steatohepatitis (MASH) are common chronic liver diseases, especially in patients with obesity and type 2 diabetes mellitus (DM2). Clinical treatment options are still limited and there are no drugs specifically indicated for MASLD or MASH. In recent years, incretin receptor agonists have gained significant popularity, which comprehensively modulate glucose homeostasis, body weight and metabolic profile of patients. Selective GLP-1 (glucagon-like peptide-1) agonists, such as semaglutide, have demonstrated the ability to reduce body weight, improve glycemic control and promote favorable metabolic adaptation. Dual GLP-1/GIP (glucose-dependent insulinotropic polypeptide) agonists, such as tirzepatide, show a synergistic effect with greater weight loss and improvements in glycemic and lipid profiles. Triple agonists of the GLP-1/GIP/GCGR (glucagon receptor), such as retatrutide, are still in early clinical trials and show high potential for significant weight loss, modulation of fat metabolism, and improvement of insulin sensitivity. All three classes of drugs are generally well tolerated, with the most common adverse effects being gastrointestinal. The risk of hypoglycemia is low except in combination with insulin or sulfonylureas. Preliminary data also suggest beneficial effects on waist circumference, blood pressure, and physical function. These studies support the use of selective, dual, and triple incretin agonists in MASLD and MASH. Future research should focus on long-term efficacy and safety monitoring, personalized patient stratification, comparison between agonist classes, and identification of predictors of therapeutic response.

Keywords: semaglutide, tirzepatide, retatrutide