{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:43:30Z","timestamp":1790621010696,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["aspenjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Parenter Enteral Nutr"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The proadaptive effects of glucagon\u2010like peptide\u20102 (GLP\u20102) include stimulation of intestinal mucosal growth as well as intestinal blood flow and angiogenesis. We have recently reported that daily subcutaneous injections of glepaglutide, a long\u2010acting GLP\u20102 analog, improved intestinal absorptive function in patients with short bowel syndrome (SBS). As secondary and exploratory end points, the effects of glepaglutide on intestinal morphology and perfusion are reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The following assessments were done in 18 patients with SBS in a randomized, crossover, dose\u2010finding, phase 2 trial before and after three weeks of treatment with glepaglutide: plasma citrulline and mucosa biopsies to assess changes in (1) intestinal morphology by immunohistochemistry and (2) gene expressions associated with absorption, proliferation, and markers of tight\u2010junction integrity by quantitative polymerase chain reaction. Intestinal perfusion was assessed in stoma nipples by laser speckle contrast imaging and quantitative fluorescence angiography with indocyanine green.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the 1\u2010 and 10\u2010mg dose groups, glepaglutide significantly increased plasma citrulline by 15.3\u2009\u00b5mol\/L (<jats:italic>P<\/jats:italic>\u2009=\u20090.001) and 15.6\u2009\u00b5mol\/L (<jats:italic>P<\/jats:italic>\u2009=\u20090.001), respectively. Trends toward an increase in villus height, crypt depth, and epithelium height were seen in the same groups. No significant changes were seen in gene expressions or intestinal perfusion.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The increase in plasma citrulline and the morphological improvements may partly account for improvement in the intestinal absorptive function. However, the finding of a stability in perfusion after three weeks of treatment with glepaglutide may have been preceded by a more profound acute\u2010phase increase in intestinal perfusion at treatment initiation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jpen.2389","type":"journal-article","created":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T13:04:42Z","timestamp":1651755882000},"page":"140-150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Effects of glepaglutide, a long\u2010acting glucagon\u2010like peptide\u20102 analog, on intestinal morphology and perfusion in patients with short bowel syndrome: Findings from a randomized phase 2 trial"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8785-9234","authenticated-orcid":false,"given":"Rahim M.","family":"Naimi","sequence":"first","affiliation":[{"name":"Department of Intestinal Failure and Liver Diseases 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