{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:51:38Z","timestamp":1788299498707,"version":"build-2803163510"},"reference-count":32,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013784","name":"Fu Jen Catholic University","doi-asserted-by":"publisher","award":["913M332-01"],"award-info":[{"award-number":["913M332-01"]}],"id":[{"id":"10.13039\/501100013784","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The One Biopharmaceutical Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Metabolic dysfunction associated steatotic liver disease (MASLD), a globally prevalent chronic liver disease, has only limited pharmacological options. Both metformin and Ganwei, health supplements containing a potent inducer of glycine N-methyltransferase (GNMT), have shown great promise for the treatment of MASLD. We conducted a 4-arm, randomized, placebo-controlled trial to investigate the safety and efficacy of metformin and Ganwei for patients with MASLD. Between September 2021 and March 2023, 64 patients with MASLD were randomly assigned at a 1:1:1:1 ratio to receive metformin alone (arm A, n = 16), a combination of metformin and Ganwei (arm B, n = 16), a placebo alone (arm C, n = 16) or Ganwei alone (arm D, n = 16) for 6 months. The primary liver steatosis outcome was assessed by control attenuation parameter (CAP) and kilopascal (kPa) scores via FibroScan. The key secondary outcomes included safety, liver function and patients\u2019 metabolic profiles. At 6 months after treatment, significant improvements in liver steatosis were observed in patients treated with Ganwei alone (repeated-measures ANOVA test, p = 0.048 and 0.048 for CAP and kPa scores, respectively) but not in patients treated with placebo and other arms. By employing a 6-point steatosis grade scale, the Ganwei alone arm exhibited a statistically significant improvement over the placebo-controlled arm (mean score 1.1 \u00b1 1.8 vs. 0.1 \u00b1 0.7, p = 0.036). Located in the promoter region of the GNMT gene, the SNP rs10948059 polymorphism is known to affect GNMT promoter activity. Interestingly, genotype analysis revealed that the improvement in liver steatosis in the Ganwei alone arm was restricted to patients harboring the T allele at GNMT rs10948059 (C\/T and T\/T vs. C\/C, p &lt; 0.05). No serious adverse events were observed in any of the treatment arms. Our study demonstrated that Ganwei may be an effective treatment option for MASLD patients. Improvement in liver steatosis by Ganwei was affected by GNMT promotor activity. Clinical trial registration: NCT06244550.<\/jats:p>","DOI":"10.3390\/ijms27052411","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T11:52:11Z","timestamp":1772711531000},"page":"2411","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Usefulness of Metformin and Ganwei for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomized, Placebo-Controlled Trial"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9890-7596","authenticated-orcid":false,"given":"Chih-Lin","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei 112, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3182-3504","authenticated-orcid":false,"given":"Wei-You","family":"Li","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical and Pharmaceutical Science, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Jung","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M. T.","family":"Chen","sequence":"additional","affiliation":[{"name":"Medical Group, University of California Davis, Sacramento, CA 95816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan Y.","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Medicine, California Northstate University, Elk Grove, CA 95757, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy Shen-Jang","family":"Fann","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6374-6905","authenticated-orcid":false,"given":"Yi-Ming Arthur","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical and Pharmaceutical Science, College of Medicine, Fu Jen Catholic University, New Taipei City 242, Taiwan"},{"name":"M. Sc. Program in Tropical Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.3748\/wjg.v20.i7.1712","article-title":"Clinical approaches to non-alcoholic fatty liver disease","volume":"20","author":"Schwenger","year":"2014","journal-title":"World J. 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