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Growth differentiation factor 15 (GDF15) belongs to the transforming growth factor beta (TGF\u2010\u03b2) superfamily and was initially identified as macrophage inhibitory cytokine\u20101 (MIC\u20101). GDF15 is considered a cytokine with an anti\u2010inflammatory effect and increases insulin sensitivity, reduces body weight, and improves clinical outcomes in diabetic patients. GDF15 acts through stimulation of glial\u2010derived neurotrophic factor (GDNF) family receptor \u03b1\u2010like (GFRAL), which is highly expressed in the brain stem to induce taste aversion. Metformin belongs to the group of biguanides that are derived from the plant <jats:italic>Galega officinalis<\/jats:italic>. It is interesting to note that metformin is an insulin\u2010sensitizing agent used as a first\u2010line therapy for T2DM that has been shown to increase the circulating level of GDF15. Thus, the present review aims to determine the critical association of the GDF15 biomarker in T2DM and how metformin agents affect it. This review illustrates that metformin activates GDF15 expression, which reduces appetite and leads to weight loss in both diabetic and nondiabetic patients. However, the present review cannot give a conclusion in this regard. Therefore, experimental, preclinical, and clinical studies are warranted to confirm the potential role of GDF15 in T2DM patients.<\/jats:p>","DOI":"10.1111\/1753-0407.13334","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T08:48:11Z","timestamp":1669711691000},"page":"806-814","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Metformin and growth differentiation factor 15 (<scp>GDF15<\/scp>) in type 2 diabetes mellitus: A hidden treasure"],"prefix":"10.1111","volume":"14","author":[{"given":"Hayder M.","family":"Al\u2010kuraishy","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Medicine, College of Medicine AL\u2010Mustansiriyah University  Baghdad Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali I.","family":"Al\u2010Gareeb","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and 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