{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T22:10:24Z","timestamp":1789596624726,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"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"}]},{"DOI":"10.13039\/100014422","name":"Eli Lilly Japan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014422","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>We aimed to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple doses of orforglipron in Japanese participants with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This was a double\u2010blind, placebo\u2010controlled, randomized, phase 1 study. In Part A, participants received single doses of orforglipron (2 or 3\u2009mg) or placebo. In Part B, participants received multiple ascending doses of daily oral orforglipron (final target doses: 12, 24, and 45\u2009mg) or placebo for 12\u2009weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Parts A and B enrolled 23 and 60 participants, respectively. The most common treatment\u2010emergent adverse events were gastrointestinal events of mild severity. No severe or serious adverse events were reported. At week 12, median\n                      <jats:italic>t<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      was 5.92\u20138.00\u2009h, and mean terminal half\u2010life was 51.8\u201376.1\u2009h. Following multiple ascending doses, orforglipron groups had greater mean reductions from baseline to week 12 in glycemic parameters (fasting glucose: orforglipron 12\u2009mg \u221264.8\u2009mg\/dL, 24\u2009mg \u221261.1\u2009mg\/dL, 45\u2009mg \u221265.6\u2009mg\/dL, placebo 7.4\u2009mg\/dL; glycated hemoglobin: orforglipron 12\u2009mg \u22122.16%, 24\u2009mg \u22122.17%, 45\u2009mg \u22122.28%, placebo 0.67%) and body weight (orforglipron 12\u2009mg \u22122.9\u2009kg, 24\u2009mg \u22126.3\u2009kg, 45\u2009mg \u22124.8\u2009kg, placebo 0.3\u2009kg) compared with placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>In Japanese participants, safety, pharmacokinetic, and pharmacodynamic results were similar to those of previous orforglipron studies. The safety and tolerability of orforglipron were also consistent with those of other glucagon\u2010like peptide\u20101 receptor agonists. Orforglipron is a potential new treatment option for Japanese patients with type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.70157","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T17:41:32Z","timestamp":1764610892000},"page":"205-213","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A phase 1 single and multiple ascending dose study of orforglipron in Japanese participants with type 2 diabetes"],"prefix":"10.1111","volume":"17","author":[{"given":"Kenji","family":"Ohwaki","sequence":"first","affiliation":[{"name":"Eli Lilly Japan K.K.  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chino","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Yokohama Minoru Clinic  Yokohama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risa","family":"Nasu","sequence":"additional","affiliation":[{"name":"Eli Lilly Japan K.K.  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazumasa","family":"Takenouchi","sequence":"additional","affiliation":[{"name":"Eli Lilly Japan K.K.  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1691-8003","authenticated-orcid":false,"given":"Tetsuaki","family":"Hirase","sequence":"additional","affiliation":[{"name":"Eli Lilly Japan K.K.  Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01931-z"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajhp\/zxaa413"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2014879117"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)01302-8"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15150"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15184"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2302392"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14829"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12098"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2024.2193"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13650"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ijo.0801083"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-018-0728-4"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0165"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15168"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01391-w"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.14752"}],"container-title":["Journal of Diabetes Investigation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdi.70157","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jdi.70157","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jdi.70157","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T13:38:06Z","timestamp":1770039486000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jdi.70157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":17,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1111\/jdi.70157"],"URL":"https:\/\/doi.org\/10.1111\/jdi.70157","archive":["Portico"],"relation":{},"ISSN":["2040-1116","2040-1124"],"issn-type":[{"value":"2040-1116","type":"print"},{"value":"2040-1124","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-05-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}