Resmetirom (Rezdiffra) for Nonalcoholic Steatohepatitis (NASH): Insights and Guidelines
Resmetirom: A New Treatment for NASH/MASH
Resmetirom, marketed as Rezdiffra is set to become the first medication approved for nonalcoholic steatohepatitis (NASH) with fibrosis in adults. 📊 About 5% of US adults have NASH, now referred to as metabolic dysfunction-associated steatohepatitis (MASH) due to links with diabetes, dyslipidemia, and obesity. Until now, lifestyle changes and medications like pioglitazone (Actos) and semaglutide (Ozempic) have been the main treatments.
- Resmetirom (Rezdiffra) activates thyroid hormone receptor-beta in the liver, enhancing liver fat metabolism and reducing fat accumulation.
- After 12 months, resmetirom plus diet and exercise resolves MASH in about 1 in 6 patients versus placebo, and about 1 in 10 see improved fibrosis.
Outcomes are based on short-term data, making it too soon to confirm if resmetirom decreases risks of cirrhosis, liver transplant, or death. Head-to-head data are lacking, and many trials are ongoing. Limited evidence shows semaglutide (Ozempic) or tirzepatide (Mounjaro) resolves MASH in about 1 in 3 patients treated versus placebo but does not yet improve fibrosis.
Specialist recommendations
- Specialists may reserve resmetirom for patients with moderate to advanced liver fibrosis despite optimizing diet, exercise, and managing comorbidities.
- GI side effects (diarrhea, nausea) may persist; patients should report severe GI pain, indicating rare gallbladder problems.
- Periodic liver function monitoring is essential.
Resmetirom can cause liver injury. Patients should report nausea or jaundice. Typically, 💊 those under 100 kg will get 80 mg/day, and those over 100 kg will get 100 mg/day. Be aware of interactions: limit statin use with resmetirom to a max of 20 mg/day of rosuvastatin (Crestor) or simvastatin (Zocor), or 40 mg/day of pravastatin (Pravachol) or atorvastatin (Lipitor).
Take-home pointsResmetirom (Rezdiffra) emerges as a promising treatment for NASH...
- Recognize resmetirom as the first approved medication for NASH with fibrosis in adults.
- Understand the activation of thyroid hormone receptor-beta enhances liver fat metabolism.
- Note that 12 months of resmetirom plus diet and exercise resolves MASH in 1 in 6 patients.
- Anticipate specialists reserving resmetirom for patients with moderate to advanced liver fibrosis.
- Monitor liver function periodically to detect potential injury from resmetirom.
- Report gastrointestinal side effects, including diarrhea and nausea, promptly.
- Administer resmetirom at 80 mg/day for patients under 100 kg and 100 mg/day for those 100 kg or more.
References
- Harrison SA, Bedossa P, Guy CD, et al. A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis. N Engl J Med. 2024;390(6):497-509. doi:10.1056/NEJMoa2309000
- European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-1402. doi:10.1016/j.jhep.2015.11.004
- Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835. doi:10.1097/HEP.0000000000000323
- Cusi K, Isaacs S, Barb D, et al. American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings: Co-Sponsored by the American Association for the Study of Liver Diseases (AASLD). Endocr Pract. 2022;28(5):528-562. doi:10.1016/j.eprac.2022.03.010
Keywords: Resmetirom, NASH, MASH, Nonalcoholic steatohepatitis, Liver fibrosis, Thyroid hormone receptor-beta, Liver fat metabolism, Semaglutide, Pioglitazone, Liver function monitoring, Statin interaction, GI side effects, Cirrhosis risk.
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