{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T01:50:47Z","timestamp":1788141047687,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,6,1]],"date-time":"2023-06-01T00:00:00Z","timestamp":1685577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1\u201016\u2010ICTS\u2010112"],"award-info":[{"award-number":["1\u201016\u2010ICTS\u2010112"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["P30DK072488"],"award-info":[{"award-number":["P30DK072488"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK130238"],"award-info":[{"award-number":["R01DK130238"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["T32DK098107"],"award-info":[{"award-number":["T32DK098107"]}],"id":[{"id":"10.13039\/100000062","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":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Glucagon\u2010like peptide\u20101 receptor agonists provide multiple benefits to patients with type 2 diabetes, including improved glycaemic control, weight loss and decreased risk of major adverse cardiovascular events. Because drug responses vary among individuals, we initiated investigations to identify genetic variants associated with the magnitude of drug responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Exenatide (5\u2009\u03bcg, subcutaneously) or saline (0.2\u2009ml, subcutaneously) was administered to 62 healthy volunteers. Frequently sampled intravenous glucose tolerance tests were conducted to assess the impact of exenatide on insulin secretion and insulin action. This pilot study was a crossover design in which participants received exenatide and saline in random order.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Exenatide increased first phase insulin secretion 1.9\u2010fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.9\u2009\u00d7\u200910\n                      <jats:sup>\u22129<\/jats:sup>\n                      ) and accelerated the rate of glucose disappearance 2.4\u2010fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20092\u2009\u00d7\u200910\n                      <jats:sup>\u221210<\/jats:sup>\n                      ). Minimal model analysis showed that exenatide increased glucose effectiveness (S\n                      <jats:sub>g<\/jats:sub>\n                      ) by 32% (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u2009.0008) but did not significantly affect insulin sensitivity (S\n                      <jats:sub>i<\/jats:sub>\n                      ). The exenatide\u2010induced increase in insulin secretion made the largest contribution to interindividual variation in exenatide\u2010induced acceleration of glucose disappearance while interindividual variation in the drug effect on S\n                      <jats:sub>g<\/jats:sub>\n                      contributed to a lesser extent (\u03b2\u2009=\u20090.58 or 0.27, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This pilot study provides validation for the value of a frequently sampled intravenous glucose tolerance test (including minimal model analysis) to provide primary data for our ongoing pharmacogenomic study of pharmacodynamic effects of semaglutide (NCT05071898). Three endpoints provide quantitative assessments of the effects of glucagon\u2010like peptide\u20101 receptor agonists on glucose metabolism: first phase insulin secretion, glucose disappearance rates and glucose effectiveness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15143","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T06:24:37Z","timestamp":1685687077000},"page":"2586-2594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Acute pharmacodynamic responses to exenatide: Drug\u2010induced increases in insulin secretion and glucose effectiveness"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7500-7854","authenticated-orcid":false,"given":"Simeon I.","family":"Taylor","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Endocrinology Diabetes, and Nutrition, University of Maryland School of 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Shahidzadeh","family":"Yazdi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology Diabetes, and Nutrition, University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilary B.","family":"Whitlatch","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology Diabetes, and Nutrition, University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Braxton D.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology Diabetes, and Nutrition, University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Shuldiner","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology Diabetes, and 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