MASH/MASLD Treatment Landscape 2026: What's Actually Working
Metabolic dysfunction-associated steatotic liver disease has gone from zero approved drugs to a crowded translation pipeline since {{resmetirom}} won FDA approval in March 2024. Best-evidence interventions remain weight loss and {{GLP-1 agonists}}; resmetirom is the only approved disease-modifying agent; FGF21 mimetics, DGAT2 antisense, and senolytics are in various trial stages.
MASLD (metabolic dysfunction-associated steatotic liver disease, formerly NAFLD) affects roughly 30-40% of adults in developed countries. Its inflammatory progression MASH (formerly NASH) advances through fibrosis to cirrhosis and ultimately liver failure or hepatocellular carcinoma. Until March 2024 there were zero FDA-approved drugs and the standard advice was weight loss, exercise, and treatment of underlying metabolic syndrome. The gold-standard intervention remains weight loss of at least 10% of body weight, which reduces hepatic fat, inflammation, and fibrosis with the strongest evidence base. GLP-1 agonists such as semaglutide and tirzepatide have produced strong off-label results; the Phase 3 ESSENCE trial reported 63% MASH resolution at 72 weeks with semaglutide. Retatrutide, a triple GLP-1/GIP/glucagon agonist, is showing similar fat-reduction effects in trials without the toxicity profile of experimental senolytics. Resmetirom (Rezdiffra), a liver-selective thyroid hormone receptor-β agonist, became the first FDA-approved MASH drug in March 2024. The MAESTRO-NASH trial reported 26-30% MASH resolution and 24-26% fibrosis improvement at 52 weeks for biopsy-confirmed F2-F3 patients. Further back in the pipeline: FGF21 mimetics (efruxifermin, pegozafermin) have shown positive Phase 2 fibrosis data; ION224, a DGAT2 antisense, reported Phase 2 fat and inflammation reductions in 2025; a Barcelona group reported a pemafibrate-plus-telmisartan combination in animals in April 2026. D+Q senolytics have biomarker-level Phase 1 data but no MASH-specific outcome data; navitoclax-based senolytics remain mouse-only because of the drug's toxicity. The senolytic angle is one of six or seven active translation tracks rather than the leading candidate.