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By combining physiological treatment endpoints with plasma proteomic profiling (PPP), we aimed to identify biomarkers to advance non\u2010invasive metabolic monitoring of compound treatment success and exploration of ulterior treatment effects on an individual basis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>We performed metabolic phenotyping along with PPP in body weight\u2010matched male and female diet\u2010induced obese (DIO) mice treated for 21\u2009days with phosphate\u2010buffered saline, single GIP and GLP\u20101 mono\u2010agonists, or a GLP\u20101\/GIP co\u2010agonist.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GLP\u20101R\/GIPR co\u2010agonism improved obesity, glucose intolerance, non\u2010alcoholic fatty liver disease (NAFLD) and dyslipidaemia with superior efficacy in both male and female mice compared with mono\u2010agonist treatments. PPP revealed broader changes of plasma proteins after GLP\u20101\/GIP co\u2010agonist compared with mono\u2010agonist treatments in both sexes, including established and potential novel biomarkers for systemic inflammation, NAFLD and atherosclerosis. Subtle sex\u2010specific differences have been observed in metabolic phenotyping and PPP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We herein show that a recently developed unimolecular GLP\u20101\/GIP co\u2010agonist is more efficient in improving metabolic disease than either mono\u2010agonist in both sexes. PPP led to the identification of a sex\u2010independent protein panel with the potential to monitor non\u2010invasively the treatment efficacies on metabolic function of this clinically advancing GLP\u20101\/GIP co\u2010agonist.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14215","type":"journal-article","created":{"date-parts":[[2020,10,1]],"date-time":"2020-10-01T11:13:00Z","timestamp":1601550780000},"page":"195-207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Plasma proteome profiles treatment efficacy of incretin dual agonism in diet\u2010induced obese female and male mice"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6745-2584","authenticated-orcid":false,"given":"Stephan","family":"Sachs","sequence":"first","affiliation":[{"name":"Institute for Diabetes and Regeneration, Helmholtz Diabetes Center at Helmholtz Centre Munich German Research Center 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