Authors: Raghad Ahmed Y Al Ameer , Khaled Saad A. Alshehri , Rahma Bin Mosa , Rasil Essa M Alqahtani , Hazim Nasser Alahmadi , Yasmin Abdulraheem Abdulaziz , Retaj Majed Almabadi , Yusra Hasan AlAbbasi , Taif Mohammed Alharbi , Norah Naffaa Alamri , Areej Mohammedali Munshi

Abstract

Background: Metabolic dysfunction-associated steatohepatitis (MASH), the progressive inflammatory form of metabolic dysfunction-associated steatotic liver disease (MASLD), is associated with fibrosis progression, cirrhosis, and liver-related morbidity and mortality. The growing burden of MASLD/MASH has accelerated development of targeted therapies, including thyroid hormone receptor beta (THR-β) agonists. This study aimed to characterize the registered clinical trial landscape of THR-β agonists for MASLD/MASH and identify major development trends and evidence gaps.

Methods: A registry-based descriptive analysis was conducted using a ClinicalTrials.gov dataset current through July 2026. Thirty-two candidate records were manually screened, and 18 interventional trials involving MASLD/MASH-spectrum populations were included after excluding healthy-volunteer pharmacology studies, non-liver indications, observational studies, and unrelated records. Trials were characterized by study status, start period, clinical phase, drug family, therapeutic strategy, clinical focus, sponsorship, geographic distribution, and results-posting status. Categorical variables were summarized using frequencies and percentages, and Fisher’s exact test assessed the association between study status and results posting.

Results: Resmetirom/MGL-3196 was the most frequently investigated THR-β agonist, accounting for 9 of 18 studies (50.0%), followed by ASC41/ASC43F with 4 studies (22.2%). Ten trials (55.6%) were phase 2, phase 2a, or phase 2b. Most were industry-sponsored (17/18, 94.4%), and 15 trials (83.3%) represented predominantly single-agent THR-β strategies. Eight trials (44.4%) were completed, 5 (27.8%) were recruiting, and 4 (22.2%) were active but not recruiting. Only 2 trials (11.1%) had posted results. Study status was not significantly associated with results posting (Fisher’s exact test, P = 0.531).

Conclusion: THR-β agonist development for MASLD/MASH is active and increasingly diversified, with resmetirom/MGL-3196 representing the largest program. However, registry results posting remains limited. These findings highlight persistent gaps in evidence dissemination and trial diversity worldwide. Greater transparency, broader geographic and academic participation, continued evaluation of combination strategies, and longer-term efficacy and safety assessment are needed to strengthen the evidence base.

Keywords: Metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis, thyroid hormone receptor beta, THR-β agonists, ClinicalTrials.gov, clinical trials.