{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:42:16Z","timestamp":1772160136672,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To address the need for noninvasive alternatives to metabolic surgery or duodenal exclusion devices for the management of type 2 diabetes (T2D) and obesity by developing an orally administered therapeutic polymer, GLY\u2010200, designed to bind to and enhance the barrier function of mucus in the gastrointestinal tract to establish duodenal exclusion noninvasively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>A Phase 1, randomized, double\u2010blind, placebo\u2010controlled, single\u2010 (SAD) and multiple\u2010ascending\u2010dose (MAD) healthy volunteer study was conducted. In the SAD arm, four cohorts received a single dose of 0.5\u2009g up to 6.0\u2009g GLY\u2010200 or placebo, while in the MAD arm, four cohorts received 5\u2009days of twice\u2010daily or three\u2010times\u2010daily dosing (total daily dose 2.0\u2009g up to 6.0\u2009g GLY\u2010200 or placebo). Assessments included safety and tolerability (primary) and exploratory pharmacodynamics, including serum glucose, insulin, bile acids and gut hormones.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>No safety signals were observed; tolerability signals were limited to mild to moderate dose\u2010dependent gastrointestinal events. In the MAD arm (Day 5), reductions in glucose and insulin and increases in bile acids, glucagon\u2010like peptide\u20101, peptide YY and glicentin, were observed following a nonstandardized meal in subjects receiving twice\u2010daily dosing of 2.0 g GLY\u2010200 (N\u2009=\u20099) versus those receiving placebo (N\u2009=\u20098).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GLY\u2010200 is safe and generally well tolerated at doses of \u22642.0\u2009g twice daily. Pharmacodynamic results mimic the biomarker signature observed after Roux\u2010en\u2010Y gastric bypass and duodenal exclusion devices, indicating a pharmacological effect in the proximal small intestine. This study represents the first clinical demonstration that duodenal exclusion can be achieved with an oral drug and supports further development of GLY\u2010200 for the treatment of obesity and\/or T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15066","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T22:40:46Z","timestamp":1687992046000},"page":"2447-2456","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["First\u2010in\u2010human study of a pharmacological duodenal exclusion therapy shows reduced postprandial glucose and insulin and increased bile acid and gut hormone concentrations"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9883-6847","authenticated-orcid":false,"given":"Mark S.","family":"Fineman","sequence":"first","affiliation":[{"name":"Glyscend Therapeutics, Inc.  Lowell Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6147-2157","authenticated-orcid":false,"given":"Christine L. N.","family":"Bryant","sequence":"additional","affiliation":[{"name":"Glyscend Therapeutics, Inc.  Lowell Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Colbert","sequence":"additional","affiliation":[{"name":"Glyscend Therapeutics, Inc.  Lowell Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8370-6102","authenticated-orcid":false,"given":"Thomas H.","family":"Jozefiak","sequence":"additional","affiliation":[{"name":"Glyscend Therapeutics, Inc.  Lowell Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John S.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Glyscend Therapeutics, Inc.  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