{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:30:52Z","timestamp":1786966252564,"version":"build-2736575974"},"reference-count":25,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sumitomo Pharma Co., Ltd."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Pers. Med.","JPM"],"abstract":"<jats:p>Background: Imeglimin is a novel oral antidiabetic agent that improves mitochondrial function and glucose metabolism in patients with type 2 diabetes mellitus (T2DM). Its effects on liver enzymes remain unclear. We investigated the effects of imeglimin on hepatic biomarkers, particularly \u03b3-glutamyl transpeptidase (\u03b3-GTP), and the reversibility of these changes after treatment discontinuation. Methods: This post hoc analysis of the prospective INFINITY Study included 25 patients with T2DM who completed 6 months of imeglimin treatment followed by a 3-month withdrawal period. Clinical parameters were averaged within predefined 3-month study phases. Changes during treatment and after discontinuation were analyzed. Results: Imeglimin significantly improved glycemic control. The geometric mean \u03b3-GTP decreased from 36.2 (27.1\u201348.4) U\/L during the Baseline Phase to 31.1 (23.5\u201341.1) U\/L during the Late Treatment Phase (p &lt; 0.05). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) also showed downward trends, although these changes were not statistically significant. During the Withdrawal Phase, \u03b3-GTP returned to 35.6 (26.4\u201348.5) U\/L (p &lt; 0.05 vs. Late Treatment Phase). Patients with baseline \u03b3-GTP &gt;50 U\/L showed larger but non-significant changes. Changes during treatment and after discontinuation were inversely correlated (r = \u22120.480, p = 0.015). Only total cholesterol correlated with \u03b3-GTP during both treatment (r = 0.554, p = 0.005) and withdrawal (r = 0.450, p = 0.024). Conclusions: \u03b3-GTP levels showed a significant decrease during imeglimin treatment and increased during the post-treatment observation period in patients with T2DM. Exploratory analyses identified an association between changes in \u03b3-GTP and total cholesterol; however, these findings should be interpreted cautiously and require confirmation in prospective studies with prespecified endpoints.<\/jats:p>","DOI":"10.3390\/jpm16080433","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:00:05Z","timestamp":1786964405000},"page":"433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Imeglimin-Associated Temporal Changes in \u03b3-Glutamyl Transferase and Total Cholesterol: A Post Hoc Exploratory Analysis of the INFINITY Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Takeshi","family":"Osonoi","sequence":"first","affiliation":[{"name":"Naka Kinen Clinic, Ibaraki 311-0113, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Shirabe","sequence":"additional","affiliation":[{"name":"Naka Kinen Clinic, Ibaraki 311-0113, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyoko","family":"Saito","sequence":"additional","affiliation":[{"name":"Naka Kinen Clinic, Ibaraki 311-0113, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Hosoya","sequence":"additional","affiliation":[{"name":"Naka Kinen Clinic, Ibaraki 311-0113, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satako","family":"Douguchi","sequence":"additional","affiliation":[{"name":"Naka Kinen Clinic, Ibaraki 311-0113, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Ofuchi","sequence":"additional","affiliation":[{"name":"Naka Kinen Clinic, Ibaraki 311-0113, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5216-0271","authenticated-orcid":false,"given":"Makoto","family":"Katoh","sequence":"additional","affiliation":[{"name":"Naka Kinen Clinic, Ibaraki 311-0113, Japan"},{"name":"Division of Research Promotion, Integrated Research Administration Center, Saitama Medical University, Saitama 350-0495, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"773","DOI":"10.2337\/db09-9028","article-title":"Banting Lecture. 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