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This study aimed to investigate whether metformin influences sarcopenia risk and evaluate the effects of potential drug targets on sarcopenia traits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed data from the National Health and Nutrition Examination Survey (NHANES) (n\u2009=\u20093549) to assess the association between metformin use and sarcopenia risk in elderly patients with type 2 diabetes. Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) from UK Biobank (n\u2009=\u20091,366,167) and FinnGen (n\u2009=\u2009218,007), with expression quantitative trait loci (eQTL) as instrumental variables, examined the causal effect of metformin-related targets on sarcopenia traits, while molecular docking explored the interaction between metformin and its drug targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Metformin use was associated with increased grip strength (OR\u2009=\u20092.46; 95% CI 1.49\u20132.38) and skeletal muscle mass (OR\u2009=\u20091.24; 95% CI 0.20\u20132.28), as well as reduced mortality (HR\u2009=\u20090.62; 95% CI 0.54\u20130.71). MR analysis suggested a possible link between GDF15 gene expression and sarcopenia traits, with no evidence of genetic confounding. Molecular docking indicated stable binding between metformin and GDF15.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study suggests that metformin may lower sarcopenia risk, particularly in elderly patients with type 2 diabetes, with GDF15 identified as a promising target for sarcopenia treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12967-025-06357-x","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T01:11:12Z","timestamp":1742519472000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Exploring the protective effect of metformin against sarcopenia: insights from cohort studies and genetics"],"prefix":"10.1186","volume":"23","author":[{"given":"Yanyan","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaonian","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoxian","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifang","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6431-4469","authenticated-orcid":false,"given":"Yun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"issue":"10","key":"6357_CR1","doi-asserted-by":"publisher","first-page":"1720 e11-e17","DOI":"10.1016\/j.jamda.2022.06.016","volume":"23","author":"N Campo-Rivera","year":"2022","unstructured":"Campo-Rivera N, Ocampo-Chaparro JM, Carvajal-Ortiz R, Reyes-Ortiz CA. 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