{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T06:30:38Z","timestamp":1791959438847,"version":"4.3.4"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Imeglimin, a novel oral antidiabetic agent, has demonstrated mitochondrial and anti-inflammatory benefits. This study evaluated the efficacy of Imeglimin-based therapies on glycemic control, mitochondrial stress (circulating cell-free mitochondrial DNA (ccf-mtDNA), and inflammation in type 2 diabetes mellitus (T2DM).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 104 T2DM patients were enrolled and assigned to one of four groups out of which 96 patients completed follow-up and data was analyzed: Imeglimin monotherapy (n=23), Imeglimin + Metformin (n=24), Imeglimin + other Oral Hypoglycemic Agents (OHAs) (n=24), and Metformin + other OHAs (n=25). Assessments at baseline and 6 months included HbA1c, lipid profile, ccf-mtDNA, NOD-like receptor family, pyrin domain containing 3 (NLRP3), Interleukins-6, 1\u03b2 and 18 (IL-6, IL-1\u03b2, and IL-18). Within-group changes were assessed using paired t-tests. Repeated measures ANCOVA models analyzed group-time interactions. Correlation analysis explored associations between \u0394 biomarkers and metabolic parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Combination therapies, particularly Imeglimin + other OHAs, significantly reduced HbA1c (\u0394=\u20130.5%, p=0.001), ccf-mtDNA (\u0394=\u201318.5 copies\/\u03bcL, p=0.02), and IL-6 (p&amp;lt; 0.001). Repeated measures ANCOVA revealed significant reductions in HbA1c (p=0.001), circulating cell-free mtDNA (p=0.004), and serum NLRP3 levels (p=0.037) across imeglimin-based therapy groups. <jats:italic>Post hoc<\/jats:italic> comparisons showed the greatest improvements in the Imeglimin + Other OHAs group versus control. Significant time \u00d7 group effects for IL-6 and IL-1\u03b2. No changes were noted in IL-18.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Imeglimin, especially in combination with non-Metformin OHAs, improves glycemic control and reduces mitochondrial and inflammatory stress in T2DM patients. These findings support its use as an adjunctive therapy with broader metabolic benefits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:uri>https:\/\/ctri.nic.in\/Clinicaltrials\/advancesearchmain.php<\/jats:uri>, identifier CTRI\/2023\/12\/060844.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1639046","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T04:13:02Z","timestamp":1758600782000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Imeglimin-based therapies improve glycemic control and reduce mitochondrial stress in type 2 diabetes: a prospective cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Abhishek","family":"Satheesan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janardanan 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