{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:36:22Z","timestamp":1784126182034,"version":"3.55.0"},"reference-count":15,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>These participant\u2010level exploratory analyses evaluated the effects of orforglipron, a once\u2010daily, orally administered non\u2010peptide glucagon\u2010like peptide\u20101 receptor agonist, versus dulaglutide and placebo, on \u03b2\u2010cell function and insulin sensitivity biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Participants (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009378) in this 26\u2010week phase 2 study with inadequately controlled type 2 diabetes (T2D) were randomly assigned to orforglipron (3, 12, 24, 36, or 45\u2009mg), dulaglutide (1.5\u2009mg), or placebo. Treatment effects on \u03b2\u2010cell function and insulin sensitivity markers were assessed, including homeostatic model assessment indices of \u03b2\u2010cell function and insulin resistance (HOMA\u2010B and HOMA\u2010IR, respectively); fasting C\u2010peptide, insulin, serum glucose, and glucagon; adiponectin; insulin\u2010like growth factor binding protein 2; proinsulin; and the proinsulin\/insulin ratio.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Orforglipron doses of 12\u2009mg and higher were associated with improved \u03b2\u2010cell function and insulin sensitivity. HOMA\u2010B increased up to 123% (C\u2010peptide) and 132% (insulin) with orforglipron doses of 12\u2009mg and higher from baseline to week 4 before stabilising. HOMA\u2010B increases were greater with all orforglipron doses than with dulaglutide. Additional \u03b2\u2010cell function biomarkers, such as fasting proinsulin and the proinsulin\/insulin ratio, also improved with orforglipron doses of 12\u2009mg and higher compared with baseline and to a greater extent than seen with dulaglutide. HOMA\u2010IR values decreased up to 16% (C\u2010peptide) and 23% (insulin) with orforglipron by week 26. Reductions in HOMA\u2010IR (insulin) were significant versus baseline only for the highest dose. IGFBP\u20102 and adiponectin, corollary biomarkers of insulin sensitivity, were generally improved with orforglipron.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increased HOMA\u2010B and improved metabolic biomarkers suggest that treatment with the orally administered non\u2010peptide GLP\u20101 receptor agonist orforglipron enhanced pancreatic \u03b2\u2010cell function and insulin sensitivity in patients with T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70022","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T07:53:43Z","timestamp":1755158023000},"page":"6314-6322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Orforglipron, an oral non\u2010peptide glucagon\u2010like peptide\u20101 receptor agonist, improves markers of \u03b2\u2010cell function and insulin sensitivity in type 2 diabetes"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8324-3275","authenticated-orcid":false,"given":"Julio","family":"Rosenstock","sequence":"first","affiliation":[{"name":"Velocity Clinical Research at Medical City  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Robins","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin L.","family":"Duffin","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzhu","family":"Lin","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiya","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Eyde","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2538-2573","authenticated-orcid":false,"given":"Christof","family":"Kazda","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manige","family":"Konig","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis 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