Rezdiffra (resmetirom) / Madrigal Pharma - LARVOL DELTA

Integrating liver and heart health: Cardiovascular risk reduction in patients with metabolic-associated steatotic liver disease. (PubMed, World J Cardiol) - "Despite progress, critical gaps persist in risk stratification tools, personalized treatment algorithms, and long-term outcomes of novel agents like resmetirom. A multidisciplinary care model, bridging hepatology and cardiology, is essential to address these challenges and improve patient outcomes."

Journal • Review • Cardiovascular • Dyslipidemia • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Dysregulation of hepatic deiodinase type I in metabolically associated steatotic liver disease. (PubMed, J Mol Endocrinol) - "Hepatic thyroid hormone action plays an important role in preventing the development and progression of metabolic liver diseases, as evidenced by the recent success of the receptor-specific agonist resmetirom...In either model, DIO1 activity was increased, but neither thyroid hormone target genes nor metabolic parameters were positively affected in the time frame of the experiment. We conclude that hepatic DIO1 biosynthesis becomes progressively disturbed with disease progression in MASLD, by a decoupling of its transcript and protein levels, highlighting the key importance of translational processes controlling Dio1 expression in hepatocytes, which are likely affected by local inflammatory mechanisms."

Journal • Gene Therapies • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • SOCS3

Pathological Evolution and Internal Medicine Management of Nonalcoholic Fatty Liver Disease (NAFLD) in the Era of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). (PubMed, Cureus) - "Lifestyle modification remains the cornerstone of management, but promising pharmacologic therapies, such as glucagon-like peptide-1 (GLP-1) receptor agonists, vitamin E, pioglitazone, and resmetirom, are emerging. With evolving nomenclature, non-invasive diagnostics, and emerging therapies, internal medicine practitioners must adopt an integrative, multidisciplinary approach to care. Future research should prioritize personalized treatment strategies and health system integration to address the growing MASLD burden."

Journal • Review • Diabetes • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • PNPLA3

Early Fibrosis Regression with Resmetirom in a Liver Transplant Recipient with De Novo MASH (WTC 2025) - "She was maintained on cyclosporine monotherapy (target trough 50-75 ng/mL). This case demonstrates early improvement in fibrosis and steatosis with resmetirom in an LT recipient with de novo MASH. While transient liver enzyme elevations occurred, they resolved spontaneously without intervention. These findings suggest potential benefits of resmetirom in this population, but longer follow-up to assess sustained benefit and larger studies to assess long-term safety and efficacy in LT recipients are needed."

Clinical • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Transplant Rejection • Transplantation • CYP3A4

Madrigal Pharmaceuticals, Inc...is leading innovation in treating metabolic dysfunction-associated steatohepatitis (MASH), previously known as NASH (Yahoo Finance) - "Looking ahead, the MAESTRO-NASH OUTCOMES trial, expected to read out in 2027, will evaluate Rezdiffra’s ability to reduce liver-related events in compensated cirrhosis patients."

P3 data • Liver Cirrhosis • Metabolic Dysfunction-Associated Steatohepatitis

Comparative Analysis of Glucagon Receptor Agonists vs Resmetirom in MASLD and MASH:Network Meta-Analysis of Clinical Trials (ENDO 2025) - "Resmetirom, a thyroid hormone receptor-β agonist, and glucagon receptor agonists (GRAs), such as Cotadutide, Retatrutide, and Survodutide, have demonstrated potential efficacy in recent clinical trials. SAE risk was not significantly elevated for Resmetirom (RR: 1.11, 95% CI: [0.77; 1.59], p = 0.58), but GRAs showed a trend toward higher SAE rates (RR: 2.38, 95% CI: [0.98; 5.82], p = 0.056).ConclusionsBoth Resmetirom and GRAs effectively reduce liver fat and ALT levels in MASLD/MASH patients, with Resmetirom offering a favorable safety profile and GRAs demonstrating superior ALT reductions but a potential increase in SAE risk. These findings underscore the promise of both therapeutic classes and highlight the need for further comparative trials to inform treatment decisions."

Retrospective data • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor

Comparative Analysis of Glucagon Receptor Agonists vs Resmetirom in MASLD and MASH:Network Meta-Analysis of Clinical Trials (ENDO 2025) - "Resmetirom, a thyroid hormone receptor-β agonist, and glucagon receptor agonists (GRAs), such as Cotadutide, Retatrutide, and Survodutide, have demonstrated potential efficacy in recent clinical trials. SAE risk was not significantly elevated for Resmetirom (RR: 1.11, 95% CI: [0.77; 1.59], p = 0.58), but GRAs showed a trend toward higher SAE rates (RR: 2.38, 95% CI: [0.98; 5.82], p = 0.056).ConclusionsBoth Resmetirom and GRAs effectively reduce liver fat and ALT levels in MASLD/MASH patients, with Resmetirom offering a favorable safety profile and GRAs demonstrating superior ALT reductions but a potential increase in SAE risk. These findings underscore the promise of both therapeutic classes and highlight the need for further comparative trials to inform treatment decisions."

Retrospective data • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor

Resmetirom for Steatotic Liver Disease: Does Data Support Widespread Use? (PubMed, Curr Gastroenterol Rep) - "Resmetirom is a liver-directed thyroid hormone receptor beta agonist that recently received accelerated approval by the FDA based on the results of the MAESTRO trial that demonstrated reasonable safety and efficacy in achieving both MASH resolution and fibrosis regression based on histological assessment. In this review, we discuss the resmetirom clinical development program, the use of noninvasive tests to select and monitor patients for treatment, and different aspects of the utility of resmetirom in the real world."

Journal • Review • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Non-invasive tests for resmetirom treatment fail to accurately define the target population: Evidence from a biopsy-proven MASLD cohort. (PubMed, Hepatol Forum) - "Therefore, performing a liver biopsy before starting resmetirom treatment will prevent unnecessary increases in cost and significantly reduce the economic burden of the treatment. Fibrosis; MASLD; MASH; non-invasive test; resmetirom."

Journal • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Thrombocytopenia

A Real-World Experience With Resmetirom: Tolerability and Access. (PubMed, Gastro Hep Adv) - "Resmetirom is a safe medication with good tolerability in regard to the side effect profile for the first 3 months. Most patients were able to gain insurance approval but delays in dispensing and insurance requirements of invasive fibrosis testing to obtain approval were observed."

Journal • Real-world evidence • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Non-invasive tests fail to ensure therapeutic precision for resmetirom in MASLD. (PubMed, Hepatol Forum) - No abstract available

Journal • Metabolic Dysfunction-Associated Steatotic Liver Disease

Non-invasive tests of fibrosis in the management of MASLD: revolutionising diagnosis, progression and regression monitoring. (PubMed, Gut) - "With the recent conditional approval of resmetirom by the US Food and Drug Administration, the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) has potentially entered a new era, requiring a comprehensive understanding of the strengths and weaknesses of non-invasive tests (NITs) for diagnosing and monitoring MASLD-related fibrosis...We suggest that future studies prioritise the validation of NITs across diverse ethnic populations. We believe it essential to explore the role of NITs in dynamic monitoring and integration of multiomics technologies, artificial intelligence and personalised risk models to improve diagnostic accuracy and treatment planning."

Journal • Review • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction-associated steatohepatitis (ENDO 2025) - "The FDA recently approved resmetirom, a liver-directed β-selective thyroid hormone receptor agonist, for MASH with significant fibrosis...Treating mice with antisense oligonucleotides (ASOs) against Coenzyme A synthase (Cosay), Cell Death-inducing DNA fragmentation factor-like effector B (CideB), hydroxysteroid 17-beta dehydrogenase 13 (Hsd17b13) or treatment with bempedoic acid or atorvastatin decreased liver lipid droplet cholesterol content and prevented CDAHFD-induced MASH and the fibrotic response...Conclusions Our findings identify cholesterol in liver lipid droplets as a critical mediator of MASH and demonstrate that COASY, CIDEB, HSD17B13 knockdown and bempedoic acid are novel therapeutic approaches to reduce liver lipid droplet cholesterol content and thereby prevent the development of MASH and liver fibrosis. In addition, this mechanism broadly links to human MASH pathogenesis and is associated with gene variants, including PNPLA3 and HSD17B13."

Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • COL1A1 • PNPLA3

Efficacy and Safety of Resmetirom in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (ENDO 2025) - "Resmetirom demonstrates promising efficacy in the treatment of MASLD, significantly reducing MRI-PDFF, LDL-C, triglycerides, lipoproteins, and liver enzymes, with no major safety concerns."

Retrospective data • Review • Cardiovascular • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Madrigal Pharmaceuticals Receives Notice of Allowance from U.S. Patent and Trademark Office for New U.S. Patent Covering Rezdiffra (Resmetirom) (GlobeNewswire) - "Madrigal Pharmaceuticals, Inc...announced that the United States Patent and Trademark Office (USPTO) has issued a Notice of Allowance covering the FDA-approved use of Rezdiffra (resmetirom), the first and only FDA-approved treatment for adults with noncirrhotic MASH (also known as NASH) with moderate to advanced liver fibrosis. The Notice of Allowance includes claims directed to Rezdiffra’s commercial weight-threshold dosing regimen as prescribed in the FDA-approved label. The U.S. patent scheduled to issue from this application provides protection through Sept. 30, 2044, and will be listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the Orange Book."

Patent • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Thyroid Hormone Analogs: Recent Developments. (PubMed, Thyroid) - "Clinical trials with MGL-3196 (resmetirom) showed significant improvement on hepatic steatosis, fibrosis, and lipids, which led to approval by the U.S. Food and Drug Administration in 2024 for the treatment of MASH. Results are currently awaited for prodrug VK2809, exerting organ specificity through prodrug conversion in the liver, ultimately targeting MASH... Ongoing strategies to enhance organ specificity of thyroid hormone analogs should include not only TR specificity but also other determinants of tissue selectivity, such as tissue-specific transporters or enzymes that activate the prodrug. This, together with the recent approval of two thyroid hormone analogs, may ensure a promising future for the development and application of thyroid hormone analogs."

Journal • Review • Cardiovascular • Dyslipidemia • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Rare Diseases

Effects of Exercise Intervention in Subjects with Metabolic Dysfunction-Associated Steatotic Liver Disease. (PubMed, J Obes Metab Syndr) - "Currently, resmetirom is the only U.S. Food and Drug Administration-approved treatment for MASLD-related fibrosis in the United States...In terms of aerobic training, traditional moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) have shown comparable benefits. This review is designed to offer refreshed perspectives on the advantages of exercise, compare the effects and mechanisms of aerobic and resistance exercise, and evaluate the advantages and disadvantages of MICT and HIIT, with emphasis on their impact on hepatic steatosis in subjects with MASLD."

Journal • Review • Fatigue • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Incretin-based Agents and Metabolic Dysfunction-associated Steatotic Liver Disease. (PubMed, Curr Pharm Des) - "Historically, treatment options for patients with more advanced stages of hepatic dysfunction (steatohepatitis, fibrosis, cirrhosis) have been limited, with only resmetirom, a thyroid hormone receptor-β agonist, recently being approved for use as a metabolic dysfunction-associated steatohepatitis (MASH)-specific treatment option...However, no incretin-based treatment is officially approved in this indication yet. This review discusses the rationale for the use of incretin-based treatment options in patients with MASLD/MASH, explaining the pathophysiological background of this disorder and describing the possible mechanism of action of these drugs."

Journal • Diabetes • Fibrosis • Genetic Disorders • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Type 2 Diabetes Mellitus

RESMETIROM: A TARGETED THYROID HORMONE RECEPTOR-Β AGONIST FOR METABOLIC-ASSOCIATED STEATOTIC LIVER DISEASE AND STEATOHEPATITIS (UEGW 2025) - No abstract available

Hepatology

Resmetirom and novel biomarkers (UEGW 2025) - No abstract available

Biomarker • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

TREATMENT WITH RESMETIROM FOR UP TO TWO YEARS LED TO IMPROVEMENT IN LIVER STIFFNESS, FIBROSIS BIOMARKERS, FIBROSIS SCORES AND PORTAL HYPERTENSION RISK IN 122 PATIENTS WITH COMPENSATED MASH CIRRHOSIS (UEGW 2025) - No abstract available

Biomarker • Clinical • Cardiovascular • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis • Portal Hypertension

USE OF NONINVASIVE TESTS (NITS) TO DIAGNOSE AND FOLLOW METABOLIC DYSFUNCTION ASSOCIATED STEATOHEPATITIS (MASH) WITH LIVER FIBROSIS PATIENTS TREATED WITH RESMETIROM (UEGW 2025) - No abstract available

Clinical • Non-invasive • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

RESMETIROM EFFECTS ON METABOLIC DYSFUNCTION ASSOCIATED STEATOHEPATITIS (MASH) WITH LIVER FIBROSIS IN PATIENTS WITH MASH GENETIC RISK ALLELES (UEGW 2025) - No abstract available

Clinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Therapeutic horizons in metabolic dysfunction-associated steatohepatitis. (PubMed, J Clin Invest) - "Recent trials with agents such as semaglutide, tirzepatide, survodutide, lanifibranor, pegozafermin, and resmetirom demonstrate substantial promise in resolving MASH and improving fibrosis, but unresolved issues remain regarding treatment duration, response heterogeneity, and long-term adherence. As the field moves toward combination therapies and precision medicine, the definition of therapeutic success will likely evolve to reflect both histological improvement and patient-reported outcomes. This Review provides a timely synthesis of the landscape, challenges, and future directions in MASH therapeutics."

Journal • Review • Diabetes • Fibrosis • Genetic Disorders • Hepatocellular Cancer • Hepatology • Immunology • Liver Failure • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity • Oncology • Solid Tumor • Type 2 Diabetes Mellitus • FASN • FGF21 • PNPLA3

Significant weight reduction with improved body composition by HDM1005, a novel long-acting GLP-1R/GIPR dual agonist (EASD 2025) - "Collectively, HDM1005 achieves significant weight loss primarily through fat mass reduction (contribution to total weight loss: 81.58%). Notably, HDM1005 also exhibits promising therapeutic potential for MASH, highlighting its dual benefit in metabolic disease management."

Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity