{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:55:54Z","timestamp":1792007754525,"version":"4.4.0"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Deanship of Research and Graduate Studies at King Khalid University, Saudi Arabia","award":["GRP\/20\/46"],"award-info":[{"award-number":["GRP\/20\/46"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant global public health issue, affecting approximately 25% of the population and currently offering limited treatment options. Trimetazidine (TMZ) serves as a metabolic modulator that shifts cellular energy metabolism from fatty acid oxidation to glucose oxidation, thereby providing a novel therapeutic strategy aimed at addressing the underlying metabolic dysfunctions that contribute to the pathogenesis of MASLD. Our study aims to assess the efficacy of trimetazidine in improving hepatic steatosis, inflammation, and various metabolic parameters. Methods: In this double-masked, randomized controlled trial, 60 patients with confirmed MASLD diagnoses were randomly assigned in a 1:1 ratio to receive either trimetazidine 20 mg three times daily or a placebo, alongside lifestyle modifications, for 24 weeks. The trial was conducted in accordance with the Declaration of Helsinki and approved by the ethics committees of both participating institutions. We measured changes in hepatic steatosis, non-invasive fibrosis scores, inflammatory markers (including interleukin-6, tumor necrosis factor-alpha, and highly sensitive C-reactive protein), liver enzymes, and lipid profiles at baseline and at the end of the 24 weeks. Results: Hepatic steatosis decreased significantly, with controlled attenuation parameter scores from 352.5 to 302 dB\/m in the TMZ group compared to the control (p &lt; 0.001). TNF-\u03b1 was reduced significantly in the TMZ group compared to the control group (p = 0.001). Fibrosis to AST score decreased from 0.49 to 0.25 in the TMZ group (p &lt; 0.001). Aspartate aminotransferase decreased significantly compared to the control group (p 0.032). Notably, TMZ also imparted cardioprotective benefits, reducing total cholesterol by 14%, LDL by 17% (both p &lt; 0.05), and triglycerides by 16% (p = 0.176). Conclusions: This groundbreaking trial supports the potential of trimetazidine as a promising therapeutic agent for MASLD, indicating substantial improvements in hepatic steatosis, inflammation, and metabolic disturbances. These findings underscore the urgency and importance of further multicenter trials to validate trimetazidine\u2019s efficacy as a disease-modifying therapy for MASLD.<\/jats:p>","DOI":"10.3390\/ph18091279","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T15:49:34Z","timestamp":1756309774000},"page":"1279","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Evaluation of the Potential Benefits of Trimetazidine in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomized Controlled Trial"],"prefix":"10.3390","volume":"18","author":[{"given":"Maha","family":"Youssif","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3077-8265","authenticated-orcid":false,"given":"Ragaey Ahmad","family":"Eid","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, and Infectious Diseases (Tropical Medicine Department), Faculty of Medicine, Beni-Suef University, Beni-Suef 62514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0432-8970","authenticated-orcid":false,"given":"Hoda","family":"Rabea","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4105-7874","authenticated-orcid":false,"given":"Yasmin M.","family":"Madney","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62521, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0064-7870","authenticated-orcid":false,"given":"Arwa","family":"Khaled","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6651-2306","authenticated-orcid":false,"given":"Khalid","family":"Orayj","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8374-2533","authenticated-orcid":false,"given":"Dina","family":"Attia","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, and Infectious Diseases (Tropical Medicine Department), Faculty of Medicine, Beni-Suef University, Beni-Suef 62514, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6359-5011","authenticated-orcid":false,"given":"Engy A.","family":"Wahsh","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy, October 6 University, Giza 12585, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1097\/TP.0000000000002480","article-title":"Nonalcoholic Fatty Liver Disease: Basic Pathogenetic Mechanisms in the Progression from NAFLD to NASH","volume":"103","author":"Pierantonelli","year":"2019","journal-title":"Transplantation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.12688\/f1000research.21918.1","article-title":"Dyslipidemia as a risk factor for liver fibrosis progression in a multicentric population with non-alcoholic steatohepatitis","volume":"9","year":"2020","journal-title":"F1000Research"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1016\/j.dsx.2020.09.026","article-title":"Pathophysiological mechanisms underlying MAFLD","volume":"14","author":"Kuchay","year":"2020","journal-title":"Diabetes. 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