{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:38:07Z","timestamp":1791499087718,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T00:00:00Z","timestamp":1767571200000},"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":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Imeglimin is a novel oral hypoglycemic agent approved for the treatment of type 2 diabetes in Japan, with dual actions to enhance insulin secretion and improve insulin sensitivity, suggested by preclinical evidence. However, the effect of imeglimin on tissue\u2010specific insulin sensitivity and glucose kinetics using glucose tracers is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      In this single\u2010arm intervention study, 22 Japanese men with type 2 diabetes received imeglimin 2000\u2009mg\/day for 20\u2009weeks. Glucose metabolism and insulin secretion were assessed by the 75\u2010g oral glucose tolerance test (OGTT) with double tracers at baseline, 1\u2009week, and 20\u2009weeks. Tissue\u2010specific insulin sensitivity and insulin clearance were also evaluated in 16 participants using a two\u2010step hyperinsulinemic\u2013euglycemic clamp before and at 20\u2009weeks. The primary endpoint was the change from baseline in the glucose area under the curve from 0 to 3\u2009h (AUC\n                      <jats:sub>0\u20133h<\/jats:sub>\n                      ) during the OGTT at 20\u2009weeks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The glucose AUC\n                      <jats:sub>0\u20133h<\/jats:sub>\n                      during the OGTT was significantly decreased at 20\u2009weeks of imeglimin administration (median change [interquartile range]: \u2212108.63 [\u2212148.25, \u221240.75] mg\u00b7h\/dL,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0002). A similar reduction was already evident at 1\u2009week. These reductions were mainly attributable to a decreased rate of oral glucose appearance. Insulin secretion indices were increased at 1 and 20\u2009weeks. Clamp studies showed improved insulin sensitivity in skeletal muscle, liver, and adipose tissue, and increased insulin clearance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/Interpretation<\/jats:title>\n                    <jats:p>These results provide the first comprehensive evidence in humans that imeglimin improves insulin secretion and insulin sensitivity in multiple tissues.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70449","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T03:55:16Z","timestamp":1767671716000},"page":"2744-2756","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dual action of imeglimin on insulin secretion and sensitivity in type 2 diabetes"],"prefix":"10.1111","volume":"28","author":[{"given":"Tsubasa","family":"Tajima","sequence":"first","affiliation":[{"name":"Department of Metabolism &amp; Endocrinology Juntendo University Graduate School of Medicine  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0579-2177","authenticated-orcid":false,"given":"Hideyoshi","family":"Kaga","sequence":"additional","affiliation":[{"name":"Department of Metabolism &amp; Endocrinology Juntendo University Graduate School of Medicine  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoaki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Metabolism &amp; Endocrinology Juntendo University Graduate School of Medicine  Bunkyo\u2010ku Tokyo 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Juntendo University Graduate School of Medicine  Bunkyo\u2010ku Tokyo Japan"},{"name":"Sportology Center Juntendo University Graduate School of Medicine  Bunkyo\u2010ku Tokyo Japan"},{"name":"Sports Medicine and Sportology Juntendo University Graduate School of Medicine  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5961-1816","authenticated-orcid":false,"given":"Hirotaka","family":"Watada","sequence":"additional","affiliation":[{"name":"Department of Metabolism &amp; Endocrinology Juntendo University Graduate School of Medicine  Bunkyo\u2010ku Tokyo Japan"},{"name":"Sportology Center Juntendo University Graduate School of Medicine  Bunkyo\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,5]]},"reference":[{"key":"e_1_2_10_2_1","volume-title":"IDF Diabetes 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