{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T14:05:51Z","timestamp":1772805951052,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,3,17]],"date-time":"2014-03-17T00:00:00Z","timestamp":1395014400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006738","name":"Faculty of Medicine, Lund University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006738","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Novartis A\/S"},{"name":"Region Sk\u00ef\u00bf\u00bdne"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      To determine the effects of dipeptidyl peptidase\u20104 (\n                      <jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\n                      \u20104) inhibition on glucagon dynamics in patients with insulin\u2010treated type 2 diabetes (\n                      <jats:styled-content style=\"fixed-case\">T2D<\/jats:styled-content>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The study was a single\u2010centre, double\u2010blind, randomized, placebo controlled crossover study in patients with\n                      <jats:styled-content style=\"fixed-case\">T2D<\/jats:styled-content>\n                      , mean age 59\u2009\u00b1\u20096 (s.d.) years and mean haemoglobin A1c 7.7\u2009\u00b1\u20090.8%, treated with exogenous insulin with or without oral antihyperglycaemic agents. Patients received vildagliptin (50\u2009mg\n                      <jats:styled-content style=\"fixed-case\">BID<\/jats:styled-content>\n                      ) or placebo as add\u2010on to insulin for 4 weeks in random order with a 4\u2010week washout in\u2010between. On day 28 of the respective treatment, patients were served a standard meal (500\u2009kcal) followed by a hyperinsulinaemic hypoglycaemic clamp (target 2.5\u2009mmol\/l) and a subsequent food re\u2010challenge (700\u2009kcal). The completers population (n\u2009=\u200929) was analysed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Glucose levels were lower with vildagliptin than with placebo during the meal [areas under the curve (\n                      <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>\n                      ) 1.23\u2009\u00b1\u20090.07 vs. 1.46\u2009\u00b1\u20090.05\u2009mol\/l min, P\u2009&lt;\u20090.001] and similar between the groups during the clamp. During the meal, glucagon levels were lower with vildagliptin (\n                      <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>\n                      1.98\u2009\u00b1\u20090.15 vs. 2.15\u2009\u00b1\u20090.17\u2009nmol\/l min, P\u2009=\u20090.016). In contrast, the glucagon counter\u2010regulation to the insulin\u2010induced hypoglycaemia was sustained by vildagliptin (6.05\u2009\u00b1\u20091.20 pmol\/l during vildagliptin vs.6.94\u2009\u00b1\u20091.09 pmol\/l during placebo,\n                      <jats:styled-content style=\"fixed-case\">NS<\/jats:styled-content>\n                      ). During the food re\u2010challenge after hypoglycaemia, glucagon levels were, again, significantly lower after vildagliptin (\n                      <jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content>\n                      1.30\u2009\u00b1\u20090.11 vs. 1.52\u2009\u00b1\u20090.12\u2009nmol\/l\u2009min, P\u2009&lt;\u20090.039). Glucagon\u2010like peptide\u20101 (\n                      <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                      \u20101) and glucose\u2010dependent insulinotropic polypeptide (GIP) levels were significantly elevated by vildagliptin compared to placebo during meal, hypoglycaemia and food re\u2010challenge.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Vildagliptin action to block\n                      <jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\n                      \u20101 and\n                      <jats:styled-content style=\"fixed-case\">GIP<\/jats:styled-content>\n                      inactivation by\n                      <jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\n                      \u20104 improves glucagon dynamics during hypoglycaemia, hyperglycaemia and food re\u2010challenge.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12284","type":"journal-article","created":{"date-parts":[[2014,2,26]],"date-time":"2014-02-26T05:32:42Z","timestamp":1393392762000},"page":"812-818","source":"Crossref","is-referenced-by-count":39,"title":["Glucagon dynamics during hypoglycaemia and food\u2010re\u2010challenge following treatment with vildagliptin in insulin\u2010treated patients with type 2 diabetes"],"prefix":"10.1111","volume":"16","author":[{"given":"J.","family":"Farngren","sequence":"first","affiliation":[{"name":"Department of Clinical Sciences Lund Lund University Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Persson","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences Malm\u00f6 Lund University Lund Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Schweizer","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. 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