THR-β Agonists Show Superiority Over Incretins for MASH Treatment

Metabolic Dysfunction-Associated Steatohepatitis (MASH), formerly known as NASH, is a severe form of fatty liver disease that can progress to cirrhosis and liver failure. Despite its growing prevalence, effective pharmacological treatments for MASH remain limited. This systematic review directly compares the efficacy and safety of two promising drug classes—Thyroid Hormone Receptor-beta (THR-β) agonists and incretin therapies—to identify which class offers superior outcomes for noncirrhotic MASH patients.

Pooled data from the reviewed studies indicated that THR-β agonists demonstrated superior efficacy in achieving MASH resolution without worsening of fibrosis. Specifically, THR-β agonists achieved MASH resolution in 55-65% of patients across studies, significantly outperforming incretin therapies which showed resolution rates of 30-40%. Both drug classes significantly improved hepatic steatosis (fat in the liver), with incretins showing a 30-50% reduction and THR-β agonists a 40-60% reduction. Furthermore, THR-β agonists consistently led to greater improvements in hepatic inflammation and ballooning degeneration. > The most critical finding was that THR-β agonists achieved a significantly higher rate of MASH resolution without fibrosis progression (pooled OR: 2.8; 95% CI: 1.9-4.1; p<0.001) compared to incretin therapies. Both classes were generally well-tolerated, though incretins were associated with higher rates of gastrointestinal adverse events (e.g., nausea, vomiting) in 15-25% of patients, whereas THR-β agonists had a lower incidence of such events, typically below 10%.