What are the most serious side effects of Resmetirom?

Resmetirom-Rezdiffra is a selective thyroid hormone receptor beta (THR-beta) agonist that was approved by the U.S. FDA in 2024 for the treatment of adult patients with non-alcoholic steatohepatitis (NASH) with moderate to severe liver fibrosis (stages F2 to F3). The emergence of this drug is regarded as a major breakthrough in the field of NASH treatment. However, although its efficacy is widely recognized by clinical and academic circles, the safety and potential serious side effects of the drug also need to be paid attention to.

Resmetirol promotes lipid metabolism and reduces liver fat accumulation by targeting the THR-β receptor in the liver, but this mechanism of action may also cause metabolism-related side effects. In published overseas data, the most serious potential adverse reactions include abnormal liver function and cholestatic liver injury. Some patients may experience elevated levels of liver enzymes such as ALT and AST in the early stages of treatment, which is usually related to the metabolic activation effect of the drug. If not monitored promptly, drug-induced hepatitis or liver damage may develop in rare cases. Therefore, the FDA recommends regular testing of liver function before medication and during treatment, which is especially important for patients with other metabolic diseases.

In addition, another adverse reaction of resmetirol that deserves vigilance is thyroid dysfunction. Although the drug mainly acts on beta subtype receptors and theoretically avoids adverse effects on the heart and central system, a few patients still report mild thyroid stimulation, such as decreased TSH and mild increase in thyroxine. This condition is mostly reversible and can return to normal once the drug is stopped or the dose is adjusted.

Digestive system reactions are also common, including diarrhea, nausea, and mild bloating. These side effects usually subside after several weeks of continued use. Compared with other systemic drugs, the incidence of serious adverse reactions of rismetirol is lower, but clinical practice still emphasizes the principle of "safety monitoring first".

Reference materials:https://www.drugs.com/monograph/resmetirom.html