{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:31:05Z","timestamp":1791873065065,"version":"4.3.4"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>GZR18, a novel long\u2010acting GLP\u20101 receptor agonist, has demonstrated substantial metabolic improvements in diabetic and obese animal models. The present studies aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of the ascending dose of GZR18 in healthy American and Chinese subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>In these phases 1, randomized, double\u2010blind, placebo\u2010controlled, sequential, dose\u2010escalation US and Chinese studies, healthy American and Chinese adults with similar age were enrolled to once\u2010weekly subcutaneous injection of GZR18 or placebo. The studies included three cohorts of male American subjects (cohorts US\u20101\u20133) and six cohorts of Chinese subjects (cohorts CN\u20101\u20136, male and female), each with a specified target dose of GZR18 ranging from 1 to 50\u2009\u03bcg\/kg (1\u201310\u2009\u03bcg\/kg for US study and 5\u201350\u2009\u03bcg\/kg for Chinese study). The primary endpoints were the safety and tolerability of GZR18. Blood samples were collected for PK and PD analysis of GZR18 before and after dosing. A population PK analysis of GZR18 was conducted to ascertain whether there are ethnic PK differences between American and Chinese adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The exposure of GZR18 was comparable between healthy American and Chinese subjects, with the geometric mean ratio between the two populations for AUC\n                      <jats:sub>0\u2010t<\/jats:sub>\n                      and\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      close to 1. A dose\u2010dependent increase in AUC\n                      <jats:sub>0\u2013t<\/jats:sub>\n                      and\n                      <jats:italic>C<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      occurred in both populations. The median time to maximum plasma concentrations (\n                      <jats:italic>T<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ) in American subjects ranged from 72 to 96\u2009h, and the mean\n                      <jats:italic>T<\/jats:italic>\n                      <jats:sub>max<\/jats:sub>\n                      ranged from 60 to 72\u2009h in Chinese subjects. The half\u2010life of GZR18 was approximately 7\u2009days in both American and Chinese subjects. Evident body weight reduction was observed in GZR18 treatment groups in Chinese subjects (cohorts CN\u20103\u20136 on Day 15, \u22121.25 to \u22121.86\u2009kg; \u22121.88% to \u22123.11%). No deaths, serious adverse events or hypoglycaemia were reported. Decreased appetite and nausea were the most frequently reported treatment\u2010emergent adverse events, observed in Chinese study and mild in severity. The safety profile of GZR18 was generally consistent with the same class of drugs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GZR18 demonstrates good tolerability in healthy American and Chinese subjects. No ethnic differences were observed between healthy American and Chinese subjects. The safety, PK and PD profiles of GZR18 support its further clinical evaluation for glycaemic and body weight control.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.16285","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T06:53:15Z","timestamp":1741589595000},"page":"2777-2789","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The safety, tolerability, pharmacokinetics and pharmacodynamics of\n                    <scp>GZR18<\/scp>\n                    in healthy American and Chinese adult subjects"],"prefix":"10.1111","volume":"27","author":[{"given":"Yue","family":"Liu","sequence":"first","affiliation":[{"name":"Clinical Trial Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine Chinese Academy of Medical Sciences  Beijing 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