{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:42:46Z","timestamp":1772160166012,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Incretin agonists are used to treat obesity and metabolic dysfunction. Instead of systemically delivering high levels of hormone receptor agonists that can lead to adverse effects, we tested and optimized oral microbead formulations that activate endogenous enteroendocrine signalling systems via distal nutrient\u2010sensing cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We report two randomized Phase 1 studies (NCT05713773 and NCT05737927) measuring acute pharmacokinetic\/pharmacodynamic responses following consumption of microbeads that deliver glucose to the distal small intestine: these studies compared coating variations and glucose dosing. The primary endpoint was plasma glucagon\u2010like peptide 1 (GLP\u20101) levels; we also measured GLP\u20102, PYY, glicentin, oxyntomodulin, glucose\u2010dependent insulinotropic peptide, C\u2010peptide, and insulin as exploratory endpoints. In a subsequent randomized Phase 2a trial (NCT05803772), prediabetic subjects consumed a lead formulation or placebo once daily for 6\u2009weeks each in a two\u2010period, two\u2010sequence crossover design. Oral glucose tolerance was measured at baseline and following treatment in each sequence, with the primary endpoint being the change in the area under the curve.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Our microbead formulation successfully targeted the distal small intestine and elicited a robust plurihormonal enteroendocrine response; our Phase 2a data show that the lead formulation improved glucose tolerance in pre\u2010diabetic patients, comparable to results using GLP\u20101 mimetics. Adverse events were infrequent and modest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Targeted glucose release activates endogenous enteroendocrine signalling networks, improves a clinically relevant metabolic endpoint, and has minimal adverse effects. The approach to target native enteroendocrine signalling has disruptive potential for the treatment of metabolic disorders, including obesity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70135","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T09:13:59Z","timestamp":1758100439000},"page":"7344-7354","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Coated glucose microbeads stimulate enteric hormone release and improve glucose tolerance in Phase 1 and 2 clinical trials"],"prefix":"10.1111","volume":"27","author":[{"given":"Kai","family":"Deusch","sequence":"first","affiliation":[{"name":"Department of Physiology University of Toronto  Toronto Canada"},{"name":"Aphaia Pharma AG  Zug Switzerland"},{"name":"Aphaia Pharma US LLC  San Juan Puerto Rico USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur","family":"Deboek","sequence":"additional","affiliation":[{"name":"Galephar Pharmaceutical Research Inc.  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