{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:52:22Z","timestamp":1790866342113,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"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":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Semaglutide has previously been approved for weight management and cardiovascular disease as a subcutaneous formulation, and more recently also as an oral formulation. However, there is limited information across oral dose levels, and there are no studies for the 25\u2009mg dose in people with obesity and type 2 diabetes (T2D). To fulfil health authority approval requirements, population pharmacokinetic and exposure\u2013response analyses were used to extrapolate efficacy and safety data from subcutaneous to oral semaglutide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Once\u2010daily oral semaglutide 25\u2009mg was approved for obesity treatment based on historical semaglutide data and the OASIS programme. Two studies were simulated: a modelled\/virtual Phase 2 trial to establish efficacy across different oral semaglutide dose levels, and a modelled\/virtual Phase 3 trial to assess efficacy in a population with overweight\/obesity and T2D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Most participants (82.2%) treated with oral semaglutide 25\u2009mg in OASIS 4 achieved exposure levels within the same range as participants treated with once\u2010weekly subcutaneous semaglutide 2.4\u2009mg in STEP 1. In the simulated studies, oral semaglutide 25\u2009mg provided significantly greater weight reduction compared with placebo, for the trial product estimand and treatment policy estimand, respectively, in those with overweight\/obesity and T2D (9.4% and 7.8%), and in those with overweight\/obesity without T2D (16.3% and 14.7%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Estimated exposure levels and efficacy observed with oral semaglutide 25\u2009mg were similar to those obtained with subcutaneous semaglutide 2.4\u2009mg, supporting application of oral semaglutide 25\u2009mg to treat individuals with overweight\/obesity, with\/without T2D.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70769","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:12:05Z","timestamp":1776935525000},"page":"5982-5991","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy, Safety and\n                    <scp>PK<\/scp>\n                    of Once\u2010Daily Oral Semaglutide 25\u2009mg for Obesity With and Without Type 2 Diabetes in Comparison With Subcutaneous Semaglutide 2.4\u2009mg: A Model\u2010Informed Drug Development Approach"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7095-4270","authenticated-orcid":false,"given":"Rune Viig","family":"Overgaard","sequence":"first","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7554-5035","authenticated-orcid":false,"given":"Oscar","family":"Birkhan","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naveen","family":"Rathor","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Spars\u00f8","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1598-2591","authenticated-orcid":false,"given":"Anders","family":"Strathe","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S  S\u00f8borg Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0111-1530","authenticated-orcid":false,"given":"Sean","family":"Wharton","sequence":"additional","affiliation":[{"name":"University of Toronto, York University, McMaster University, Wharton Weight Management Clinic  Burlington Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Rubino","sequence":"additional","affiliation":[{"name":"Washington Center for Weight Management and Research  Arlington Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1614362"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2008.102"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP161365.GL"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000442721"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.645507"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(23)01185\u20106"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2032183"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2500969"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14863"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(21)00213\u20100"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(21)00174\u20101"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(23)01127\u20103"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(17)30013\u2010x"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17\u20100417"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(17)30092\u2010x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19\u20100749"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(20)30075\u20109"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.2942"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2213\u20108587(19)30192\u20105"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19\u20100898"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19\u20100883"},{"key":"e_1_2_12_23_1","unstructured":"FDA \u201cWegovy PI \u201d(2025) https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/218316Orig1s000lbl.pdf."},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2025.3599"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(22)00008\u20100"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13773"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15211"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300\u2010018\u20100458\u20105"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010021\u201001025\u2010x"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100387"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aar7047"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010018\u20100668\u2010z"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13300\u2010019\u20100581\u2010y"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.2165\/11631900\u2010000000000\u201000000"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20108587(25)00226\u20108"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13358"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.70769","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.70769","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.70769","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T07:34:00Z","timestamp":1786088040000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.onlinelibrary.wiley.com\/doi\/10.1111\/dom.70769"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":35,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/dom.70769"],"URL":"https:\/\/doi.org\/10.1111\/dom.70769","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]},"assertion":[{"value":"2026-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}