Resmetirom (Rezdiffra)
Resmetirom is the first FDA-approved therapy (March 2024) for noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate-to-advanced liver fibrosis (F2–F3). Approval was based on the MAESTRO-NASH trial.
- Mechanism of action
- Liver-directed thyroid hormone receptor beta (THR-β) selective agonist, reducing hepatic fat and improving markers of fibrosis in metabolic dysfunction-associated steatohepatitis (MASH).
- Administration route
- Oral, once daily
FDA-approved indications (2026)
Noncirrhotic MASH with significant fibrosis
Adults with MASH and moderate-to-advanced liver fibrosis (consistent with stages F2 to F3), in conjunction with diet and exercise. Not for F4 (cirrhosis).
Dosing: adult, renal, and hepatic
| Population | Dose |
|---|---|
| Weight <100 kg | 80 mg PO once daily. |
| Weight ≥100 kg | 100 mg PO once daily. |
| Hepatic impairment | Avoid in decompensated cirrhosis (Child-Pugh B/C). Reduce dose in certain impairment scenarios per label. |
| Renal impairment | Severe renal impairment — reduce dose per label; not studied in dialysis. |
Contraindications and boxed warnings
Contraindications
- Decompensated cirrhosis.
- Concomitant strong CYP3A4 inhibitors or certain OATP1B1/1B3 inhibitors per label.
2026 guideline and pivotal trial position
AASLD 2024 and 2025 MASH practice guidance position resmetirom as the first approved pharmacotherapy for F2/F3 MASH, layered on metabolic management (weight loss, SGLT2 inhibitors, GLP-1 RAs). Liver biopsy is no longer strictly required in 2026 for treatment eligibility if noninvasive tools consistently indicate F2/F3 disease (flagged: 2026-uncertain — biopsy expectations evolving).
MAESTRO-NASH (2024)
Higher rates of MASH resolution and fibrosis improvement at 52 weeks vs placebo.
Cross-system reasoning
Resmetirom connects hepatology to cardiometabolic care. Most candidates have T2DM, obesity, and ASCVD risk factors and are already on SGLT2 inhibitors, GLP-1 RAs, or statins. Drug-drug interactions with statins (especially simvastatin and rosuvastatin dose limits) require proactive medication reconciliation. Thyroid axis monitoring is appropriate because of the mechanism, though clinical hypothyroidism is not a typical effect.
Key references
Related clinical reading
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This reference is for US-licensed physicians and is not a substitute for the full FDA prescribing information. Dosing in special populations, drug interactions, and emerging safety information should be verified against the current manufacturer label and society guidelines before prescribing.