{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T02:41:54Z","timestamp":1772160114755,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,8]],"date-time":"2019-10-08T00:00:00Z","timestamp":1570492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","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":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To determine the effects of individual and combined therapies on plasma insulin, glucagon, \u03b2\u2010hydroxybutyrate (\u03b2\u2010OH) and associated metabolites.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>In DURATION\u20108, the combination of once\u2010weekly exenatide (EQW)\u2009+\u200910\u2009mg dapagliflozin (Dapa) in patients with type 2 diabetes poorly controlled with metformin\u2010reduced HbA1c levels and body weight (at weeks 28 and 52) was compared with EQW\u2009+\u2009placebo (Plb) or Dapa + Plb. The study included 678 patients randomized 1:1:1 to EQW\u2009+\u2009Dapa, EQW\u2009+\u2009Plb, or Dapa + Plb. Plasma insulin and glucagon were measured at fasting and 2\u2009hours after a mixed meal. Fasting plasma free fatty acids (FFA) and \u03b2\u2010OH concentrations were measured.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The fasting insulin\u2010to\u2010glucagon molar ratio (I\/Glg) increased with EQW\u2009+\u2009Plb only; postprandial I\/Glg increased in all groups but significantly more with EQW\u2009+\u2009Plb. \u03b2\u2010OH, FFA, and glycerol concentrations showed a parallel response: larger increments with Dapa + Plb, larger decrements with EQW\u2009+\u2009Plb, and intermediate changes with EQW\u2009+\u2009Dapa. \u03b2\u2010OH levels and I\/Glg were inversely related to one another. Patients in the top quartile of \u03b2\u2010OH changes from baseline [median (interquartile range): +207 (305) vs. \u221265 (\u2212154) \u03bcmol\/L;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u2009.0001] were more frequently treated with Dapa + Plb, had higher urine glucose\u2010to\u2010creatinine ratios, and lower fasting insulin [52 (51) vs. 68 (53) pmol\/L;\n                      <jats:italic>P<\/jats:italic>\n                      = .0013) and I\/Glg [1.76 (1.49) vs. 2.23 (1.70) mol\/mol;\n                      <jats:italic>P<\/jats:italic>\n                      = .0020]. Haematocrit increased only in the Dapa group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The EQW\u2009+\u2009Dapa combination abolished the Dapa\u2010induced rise in \u03b2\u2010OH, reduced the EQW\u2010induced increase in I\/Glg, maintained glycosuria, and increased haematocrit in patients with poorly controlled type 2 diabetes. The drug combination may preserve any putative benefits while mitigating the risk of ketoacidosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13870","type":"journal-article","created":{"date-parts":[[2019,8,30]],"date-time":"2019-08-30T05:39:29Z","timestamp":1567143569000},"page":"99-106","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hormone\u2010substrate changes with exenatide plus dapagliflozin versus each drug alone: The randomized, active\u2010controlled DURATION\u20108 study"],"prefix":"10.1111","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1384-1584","authenticated-orcid":false,"given":"Ele","family":"Ferrannini","sequence":"first","affiliation":[{"name":"CNR Institute of Clinical Physiology  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Baldi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9486-1255","authenticated-orcid":false,"given":"Juan P.","family":"Fr\u00edas","sequence":"additional","affiliation":[{"name":"National Research Institute  Los Angeles California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristian","family":"Guja","sequence":"additional","affiliation":[{"name":"Department of Diabetes Nutrition and Metabolic Diseases, Carol Davila University of Medicine and Pharmacy  Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise","family":"Hardy","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gaithersburg Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Repetto","sequence":"additional","affiliation":[{"name":"AstraZeneca  Gaithersburg 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