{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:58:15Z","timestamp":1786121895694,"version":"build-2736575974"},"reference-count":23,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T00:00:00Z","timestamp":1778371200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003500","name":"University of Padova","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003500","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":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Oral semaglutide absorption is subject to inter\u2010individual variability. We investigated whether estimated individual exposure (\n                      <jats:italic>eC<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>avg<\/jats:italic>\n                      <\/jats:sub>\n                      ) provides predictive information beyond the prescribed dose in a real\u2010world cohort of patients with type 2 diabetes (T2D).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively included patients initiating oral semaglutide to calculate\n                      <jats:italic>eC<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>avg<\/jats:italic>\n                      <\/jats:sub>\n                      at each follow\u2010up visit, using a validated population pharmacokinetic model incorporating dose, weight, sex, ethnicity and GI disorders, but without measuring plasma semaglutide concentrations. Mixed\u2010effects models were used to assess the associations of dose and\n                      <jats:italic>eC<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>avg<\/jats:italic>\n                      <\/jats:sub>\n                      with changes in HbA1c and percent body weight, and to compare model fit. For GI side effects, time\u2010adjusted fixed\u2010effects logistic regression was employed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We analysed 256 participants (31.6% women, mean age 65.6\u2009years). During a median follow\u2010up of 19\u2009months, HbA1c declined by 0.7% and body weight by 7.5%; 41.8% of patients reported GI side effects. Both dose and\n                      <jats:italic>eC<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>avg<\/jats:italic>\n                      <\/jats:sub>\n                      were significantly associated with all outcomes when analysed individually. For \u0394HbA1c, the dose model outperformed the\n                      <jats:italic>eC<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>avg<\/jats:italic>\n                      <\/jats:sub>\n                      model (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01), while\n                      <jats:italic>eC<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>avg<\/jats:italic>\n                      <\/jats:sub>\n                      showed modestly improved fit for weight loss (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). The exposure\u2010effect relationship was clearly right\u2010shifted for weight loss compared to the glycaemic effect. For GI side effects,\n                      <jats:italic>eC<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>avg<\/jats:italic>\n                      <\/jats:sub>\n                      remained significantly associated with the outcome after adjustment for dose residuals, indicating that\n                      <jats:italic>eC<\/jats:italic>\n                      <jats:sub>\n                        <jats:italic>avg<\/jats:italic>\n                      <\/jats:sub>\n                      had greater predictive value for tolerability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Although estimated and not measured, the exposure to oral semaglutide may provide outcome\u2010dependent information. While the prescribed dose seems sufficient to predict glycaemic response, estimated exposure provides additional value for weight loss and GI tolerability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70840","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T03:43:00Z","timestamp":1778470980000},"page":"6405-6412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estimated Oral Semaglutide Exposure Has Distinct Relationships With Glycaemic Response, Weight Loss and Gastrointestinal Tolerability"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6510-2097","authenticated-orcid":false,"given":"Gian Paolo","family":"Fadini","sequence":"first","affiliation":[{"name":"Department of Medicine University of Padova  Padua Italy"},{"name":"Veneto Institute of Molecular Medicine  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario Luca","family":"Morieri","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Padova  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlotta","family":"Boscaro","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Padova  Padua Italy"},{"name":"Veneto Institute of Molecular Medicine  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta Maria","family":"Bonora","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Padova  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cignarella","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Padova  Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14500"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-021-01499-w"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-022-09735-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14710"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15554"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-021-01025-x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2021.100387"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16398"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI194740"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.70613"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2025.101499"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01127-3"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc24-2425"},{"issue":"16","key":"e_1_2_10_15_1","first-page":"S335","article-title":"Efficacy of Oral Semaglutide: Overview of the PIONEER Clinical Trial Program and Implications for Managed Care","volume":"26","author":"Rodbard H. 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