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Intestinal insufficiency and IF involve deficiency of the proglucagon\u2010derived hormones glucagon\u2010like peptide\u20101 (GLP\u20101) and GLP\u20102. Two major problems of SB are epithelial surface loss and accelerated transit. Standard treatment now targets intestinal adaptation with a GLP\u20102 analogue to enlarge absorptive surface area. It is possible that additional benefit can be gained from a combination of GLP\u20101 and GLP\u20102 activity, with the aim to enlarge intestinal surface area and slow intestinal transit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The GLP\u20101\u2013 and GLP\u20102\u2013specific effects of the novel dual GLP\u20101 receptor (GLP\u20101R) and GLP\u20102 receptor (GLP\u20102R) agonist dapiglutide (rINN) were characterized in rodents. Furthermore, in a murine SB model of intestinal insufficiency with 40% ileocecal resection, the influence of dapiglutide on intestinal growth, body weight, food intake, volume status, and stool water content was tested against vehicle and sham\u2010operated male mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Dapiglutide significantly improves oral glucose tolerance, reduces intestinal transit time, and promotes intestinal growth. In the SB mouse model, dapiglutide promotes body weight recovery, despite unchanged intake of liquid diet. Dapiglutide promotes significant intestinal growth, as indicated by significantly increased villus height as well as intestinal length. Furthermore, dapiglutide reduces stool water losses, resulting in reduced plasma aldosterone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Dapiglutide possesses specific and potent GLP\u20101R and GLP\u20102R agonist effects in rodents. In the murine SB model, combined unimolecular GLP\u20101R and GLP\u20102R stimulation with dapiglutide potently attenuates intestinal insufficiency and potentially also IF.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jpen.2286","type":"journal-article","created":{"date-parts":[[2021,10,27]],"date-time":"2021-10-27T11:06:21Z","timestamp":1635332781000},"page":"1107-1118","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Dapiglutide, a novel dual GLP\u20101 and GLP\u20102 receptor agonist, attenuates intestinal insufficiency in a murine model of short bowel"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3382-3578","authenticated-orcid":false,"given":"Johannes","family":"Reiner","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Endocrinology Rostock University Medical Center  Rostock 18057 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