REZDIFFRA (resmetirom) is a first-in-class thyroid hormone receptor-beta (THR-β) agonist approved for the treatment of noncirrhotic nonalcoholic steatohepatitis (NASH) with moderate-to-advanced liver fibrosis (F2–F3). It selectively activates hepatic THR-β, reducing intrahepatic lipid accumulation, inflammation, and fibrosis while minimizing systemic effects. Approval under the FDA’s accelerated pathway is based on histopathologic improvement; confirmatory trials are required to verify clinical outcomes such as reduced cirrhosis-related morbidity.  

Key considerations include weight-based dosing, monitoring for hepatotoxicity and gallbladder adverse events, and avoidance in decompensated cirrhosis. Common adverse reactions (e.g., diarrhea, nausea) are manageable, but drug interactions with CYP2C8 inhibitors and statins necessitate dose adjustments or avoidance. Resmetirom represents a targeted therapeutic advance for a condition with previously limited treatment options.