{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T16:44:30Z","timestamp":1792341870805,"version":"4.4.0"},"reference-count":165,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T00:00:00Z","timestamp":1792281600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012131","name":"Department of Science and Technology of Liaoning Province","doi-asserted-by":"publisher","award":["2019JH6\/10100009"],"award-info":[{"award-number":["2019JH6\/10100009"]}],"id":[{"id":"10.13039\/501100012131","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medicinal Research Reviews"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Type 2 diabetes mellitus (T2DM) is a highly prevalent chronic metabolic disease worldwide, and the clinical prevention and control situation is severe. Although the various antidiabetic drugs currently in clinical use can lower blood glucose levels through different mechanisms, there are significant differences in efficacy among individuals. Existing evidence suggests that differences in gut microbiota (GM) composition and metabolic function may be one of the key factors contributing to the heterogeneity in drug efficacy. Based on this, this review describes the physiological and pathological mechanisms of the GM\u2010metabolism axis and systematically reviews the modulatory effects of different classes of antidiabetic drugs on this axis and their underlying mechanisms. Available studies suggest that metformin, \u03b1\u2010glucosidase inhibitors, dipeptidyl peptidase\u20104 inhibitors (DPP\u20104i), sodium\u2010glucose cotransporter\u20102 inhibitors (SGLT2i), thiazolidinediones (TZDs), and oral glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) may differentially affect GM composition and\/or microbial metabolites, including short\u2010chain fatty acids (SCFAs), branched\u2010chain amino acids (BCAAs), and bile acids. These alterations may be associated with glucose homeostasis and insulin resistance through pathways involving GPR41\/43, HDACs, AMPK, mTORC1\/S6K1, FXR\u2010FGF15\/19, and TGR5\u2010GLP\u20101 signaling. By integrating clinical and mechanistic evidence, this review highlights the potential contribution of the GM\u2010metabolism axis to the glucose\u2010lowering effects of antidiabetic drugs. However, the quantity and confidence of evidence vary substantially across drug classes, and causal and clinical relevance requires further validation. These findings provide a basis for future research on personalized interventions for T2DM characterized by SCFA\u2010producing bacterial deficiency, BCAA overload, or dysregulated bile acid metabolism.<\/jats:p>","DOI":"10.1002\/med.70117","type":"journal-article","created":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T16:32:16Z","timestamp":1792341136000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the Gut Microbiota\u2010Metabolism Axis: Novel Pharmacological Mechanisms and Translational Application Strategies for Oral Antidiabetic Drugs"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-7785-873X","authenticated-orcid":false,"given":"Ruodi","family":"Yang","sequence":"first","affiliation":[{"name":"First Clinical School Liaoning University of Traditional Chinese Medicine Shenyang 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