DAY 3: Resmetirom May Be More Effective in Preventing Cirrhosis than Glucagon-Like Peptide-1 Receptor Agonists

Treatment with resmetirom achieved a marked decrease in the incidence of cirrhosis compared with glucagon-like peptide-1 (GLP-1) receptor agonists in a large population living with metabolic dysfunction-associated steatohepatitis (MASH), according to real-world data presented at the 2026 Annual Scientific Meeting of the American College of Gastroenterology in Nashville, Tennessee. 

MASH is a progressive condition defined by the presence of steatosis, inflammatory processes, and hepatocyte damage that ultimately progresses to fibrosis. Within MASH pathology, the progression from severe fibrosis to cirrhotic transformation constitutes a pivotal clinical milestone in the emergence of serious hepatic complications. Both resmetirom and GLP-1 receptor agonists have recently received approval in the United States for the treatment of MASH. Resmetirom was designed to target the liver, but has also shown lipid-lowering benefits, while GLP-1 receptor agonists provide broader metabolic benefits and facilitate weight loss. 

In a retrospective, propensity-matched cohort study using U.S. electronic health record data from the TriNetX network, researchers at SUNY Upstate Medical University compared the odds of developing cirrhosis between patients with MASH treated with resmetirom and those on GLP-1 therapies. While the initial cohorts included 1080 people treated only with resmetirom and 21,319 people who were using only GLP-1 receptor agonists, propensity score matching for demographic variables and comorbidities yielded two groups of 1,067 patients each. 

Patients with MASH treated with resmetirom had lower odds of progressing to cirrhosis than GLP-1 users both before and after propensity matching. After matching, cirrhosis was detected in 3% of patients treated with resmetirom and in 7.5% of those on GLP-1 therapies. 

“Future directions would be aimed at randomized controlled trials to confirm these associations and to study long-term outcomes, such as liver-related decompensation, hepatocellular carcinoma, and liver-related mortality, as we have more time to study the effects of these drugs,” lead author Shefali Mody, MBBS, an internal medicine resident at SUNY Upstate Medical University, said during a poster presentation. 

Mody noted that the results of the analysis are likely attributed to the targeted hepatic mechanism of resmetirom, which operates through direct stimulation of THR-β receptors on hepatocytes alongside its lipid-reducing properties, thereby mitigating hepatic damage and fibrotic progression. On the other hand, GLP-1 receptor agonists function through less direct mechanisms involving broader systemic metabolic regulation.