{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:36:14Z","timestamp":1793126174572,"version":"4.5.0"},"reference-count":19,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"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","award":["LY3532226"],"award-info":[{"award-number":["LY3532226"]}],"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":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This Phase 1b, randomised, double\u2010blind clinical trial investigated the contribution of glucose\u2010dependent insulinotropic polypeptide (GIP) and glucagon\u2010like peptide\u20101 (GLP\u20101) to insulin sensitivity and secretion in people with type 2 diabetes (T2D) on metformin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Participants were randomised to receive the long\u2010acting GIP receptor agonist macupatide, dulaglutide or both combined. Insulin sensitivity (\n                      <jats:italic>M<\/jats:italic>\n                      value), insulin secretion rate (ISR) and the corresponding clamp disposition index (cDI) were assessed from hyperinsulinemic euglycaemic clamps at baseline and after 12\u2010week treatment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Overall baseline means were cDI, 0.3\u2009pmol*m\n                      <jats:sup>\u22122<\/jats:sup>\n                      *L*min\n                      <jats:sup>\u22122<\/jats:sup>\n                      *kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      ;\n                      <jats:italic>M<\/jats:italic>\n                      value, 5.8\u2009mg*kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      *min\n                      <jats:sup>\u22121<\/jats:sup>\n                      ; ISR, 116.8\u2009pmol*min\n                      <jats:sup>\u22121<\/jats:sup>\n                      *m\n                      <jats:sup>\u22122<\/jats:sup>\n                      . The 12\u2010week increases in the macupatide, dulaglutide and combination arms were, respectively: cDI, 0.2 (63.2% change), 0.5 (181.0%) and 1.0 (321.5%);\n                      <jats:italic>M<\/jats:italic>\n                      value, 1.3 (33.1%), 0.2 (10.4%) and 2.0 (38.3%); ISR, 37.6 (32.2%), 191.1 (163.6%) and 225.3 (192.9%). Macupatide alone significantly increased the\n                      <jats:italic>M<\/jats:italic>\n                      value and, to a lesser yet significant extent, ISR. Combination therapy was numerically greater than both monotherapies in augmenting all indices. The most frequent adverse events were injection site reactions and diarrhoea. Study discontinuations due to treatment\u2010emergent adverse events were uncommon. There were no deaths during the study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings demonstrate that chronic GIP receptor activation in individuals with T2D leads primarily to increased insulin sensitivity, and that combining GIP and GLP\u20101 receptor agonism can augment both insulin secretion and insulin sensitivity compared to GLP\u20101 therapy alone.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70863","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T22:29:32Z","timestamp":1780439372000},"page":"7196-7206","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Insulin Sensitivity and Beta Cell Function With Macupatide Alone or With Dulaglutide in Type 2 Diabetes: A Phase 1b, Randomised Controlled Trial"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8346-2037","authenticated-orcid":false,"given":"Tim","family":"Heise","sequence":"first","affiliation":[{"name":"Profil  Neuss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8843-5452","authenticated-orcid":false,"given":"Eric","family":"Zijlstra","sequence":"additional","affiliation":[{"name":"Profil  Neuss Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mari","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, National Research Council (CNR) of Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Roell","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8696-7500","authenticated-orcid":false,"given":"Kieren J.","family":"Mather","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4502-0470","authenticated-orcid":false,"given":"Axel","family":"Haupt","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panagiotis","family":"Flevaris","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Liao","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laiyi","family":"Chua","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Harris","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4449-6231","authenticated-orcid":false,"given":"Edward J.","family":"Pratt","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00260"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00387"},{"issue":"4","key":"e_1_2_10_4_1","first-page":"912","article-title":"Additive Insulinotropic Effects of Exogenous Synthetic Human GIP and GLP 1(7\u201036) Amide Infused at Near\u2010Physiological Insulinotropic and Glucose Concentrations","volume":"76","author":"BE N. 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