{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T09:37:29Z","timestamp":1779183449121,"version":"3.51.4"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T00:00:00Z","timestamp":1463011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      To assess the pharmacokinetics, pharmacodynamics, safety and tolerability of multiple ascending doses of the glucagon receptor antagonist\n                      <jats:styled-content style=\"fixed-case\">PF<\/jats:styled-content>\n                      \u201006291874 in patients with type 2 diabetes mellitus (\n                      <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Patients were randomized to oral\n                      <jats:styled-content style=\"fixed-case\">PF<\/jats:styled-content>\n                      \u201006291874 or placebo on a background of either metformin (Part A, Cohorts 1\u20135: 5\u2013150 mg once daily), or metformin and sulphonylurea (Part B, Cohorts 1\u20132: 15 or 30 mg once daily) for 14\u201328 days. A mixed\u2010meal tolerance test (\n                      <jats:styled-content style=\"fixed-case\">MMTT<\/jats:styled-content>\n                      ) was administered on days \u22121 (baseline), 14 and 28. Assessments were conducted with regard to pharmacokinetics, various pharmacodynamic variables, safety and tolerability. Circulating amino acid concentrations were also measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">PF<\/jats:styled-content>\n                      \u201006291874 exposure was approximately dose\u2010proportional with a half\u2010life of \u223c19.7\u201322.7 h. Day 14 fasting plasma glucose and mean daily glucose values were reduced from baseline in a dose\u2010dependent manner, with placebo\u2010corrected decreases of 34.3 and 42.4 mg\/dl, respectively, at the 150 mg dose. After the\n                      <jats:styled-content style=\"fixed-case\">MMTT<\/jats:styled-content>\n                      , dose\u2010dependent increases in glucagon and total glucagon\u2010like peptide\u20101 (\n                      <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                      \u20101) were observed, although no meaningful changes were noted in insulin, C\u2010peptide or active\n                      <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                      \u20101 levels. Small dose\u2010dependent increases in\n                      <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\n                      cholesterol were observed, along with reversible increases in serum aminotransferases that were largely within the laboratory reference range. An increase in circulating gluconeogenic amino acids was also observed on days 2 and 14. All dose levels of\n                      <jats:styled-content style=\"fixed-case\">PF<\/jats:styled-content>\n                      \u201006291874 were well tolerated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">PF<\/jats:styled-content>\n                      \u201006291874 was well tolerated, has a pharmacokinetic profile suitable for once\u2010daily dosing, and results in reductions in glucose with minimal risk of hypoglycaemia.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12672","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T08:24:16Z","timestamp":1460276656000},"page":"795-802","source":"Crossref","is-referenced-by-count":44,"title":["Effects of multiple ascending doses of the glucagon receptor antagonist\n                    <scp>PF<\/scp>\n                    \u201006291874 in patients with type 2 diabetes mellitus"],"prefix":"10.1111","volume":"18","author":[{"given":"D. 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