{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T22:26:49Z","timestamp":1790029609201,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/Hypothesis<\/jats:title>\n                    <jats:p>Initial dose\u2010escalation has been shown to mitigate gastrointestinal adverse events in people treated with incretin\u2010based medications. We aimed to analyse dose\u2010response relationships for the proportion of study participants reporting nausea and vomiting among those exposed to incretin mimetics approved for Type 2 diabetes (GLP\u20101 receptor agonists and the dual GIP\/GLP\u20101 receptor agonist tirzepatide) in Phase 1 (no or short dose escalation) and Phase 3 (with dose escalation) trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Non\u2010linear regression analysis (curve fitting) was used to estimate the dose that would elicit nausea or vomiting in 50% of exposed subjects (ED\n                      <jats:sub>50<\/jats:sub>\n                      ). We used the ratio of ED\n                      <jats:sub>50<\/jats:sub>\n                      ies determined for Phase 1 and Phase 3 trials as an indicator of developing tolerance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The development of tolerance for nausea and vomiting (indicated by a ratio of ED\n                      <jats:sub>50<\/jats:sub>\n                      ies Phase 3\/Phase 1) for semaglutide (both s.c. and oral) and for tirzepatide was significantly higher than 1. Comparing all approved incretin\u2010based medications, a higher ratio, indicating the development of more tolerance, was associated with (a) a longer drug escalation period and (b) a greater number of dose\u2010escalation steps. This ED\n                      <jats:sub>50<\/jats:sub>\n                      ratio (Phase 3\/Phase 1) was also significantly associated with effect sizes for intended therapeutic actions of incretin mimetics (reductions in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      and body weight).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/Interpretation<\/jats:title>\n                    <jats:p>Taken together, optimised dose\u2010escalation regimens may lead to greater tolerance for nausea and vomiting, which allows to use of higher doses, which are associated with greater therapeutic effectiveness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70613","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T20:06:01Z","timestamp":1773000361000},"page":"4232-4242","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dose\u2010Escalation Regimens for Incretin Mimetics in Type 2 Diabetes Are Associated With Tolerance for Nausea and Vomiting"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-6954","authenticated-orcid":false,"given":"Michael A.","family":"Nauck","sequence":"first","affiliation":[{"name":"Diabetes, Endocrinology, Metabolism Section Medical Department I Josef\u2010Hospital, Ruhr University Bochum  Bochum Germany"},{"name":"Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald  Greifswald 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