{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T02:52:43Z","timestamp":1781664763968,"version":"3.54.5"},"reference-count":29,"publisher":"American Diabetes Association","issue":"10","license":[{"start":{"date-parts":[[2020,9,21]],"date-time":"2020-09-21T00:00:00Z","timestamp":1600646400000},"content-version":"vor","delay-in-days":62,"URL":"https:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Texas Diabetes Institute\u2013University Health System"},{"DOI":"10.13039\/100008635","name":"University of Texas Health Science Center at San Antonio","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008635","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>To examine the mechanisms responsible for improved glycemia with combined sodium\u2013glucose cotransporter 2 inhibitor (SGLT2i) plus dipeptidyl peptidase 4 inhibitor therapy in type 2 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>Fifty-six patients (HbA1c 8.9 \u00b1 0.2% [74 \u00b1 2 mmol\/mol]) were randomized to dapagliflozin (DAPA) 10 mg, DAPA\/saxagliptin (SAXA) 10\/5 mg, or placebo (PCB) for 16 weeks. Basal endogenous glucose production (EGP) (3-3H-glucose), urinary glucose excretion, glucose\/lipid oxidation, HbA1c, and substrate\/hormone levels were determined before treatment (Pre-Tx) and after treatment (Post-Tx).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>At week 16, HbA1c decrease was greater (P &amp;lt; 0.05) in DAPA\/SAXA (\u22122.0 \u00b1 0.3%) vs. DAPA (\u22121.4 \u00b1 0.2%) and greater than PCB (0.2 \u00b1 0.2%). Day 1 of drug administration, EGP (\u223c2.40 mg\/kg\/min) decreased by \u22120.44 \u00b1 0.09 mg\/kg\/min in PCB (P &amp;lt; 0.05) but only by \u22120.21 \u00b1 0.02 mg\/kg\/min in DAPA and DAPA\/SAXA (P &amp;lt; 0.05 vs. PCB). At week 16, EGP increased to 2.67 \u00b1 0.09 mg\/kg\/min (DAPA) and 2.61 \u00b1 0.08 mg\/kg\/min (DAPA\/SAXA), despite reductions in fasting plasma glucose by 47 and 77 mg\/dL, respectively, and no changes in PCB. Baseline plasma free fatty acids rose by 40 \u00b5mol\/L with DAPA but declined by \u2212110 with PCB and \u221290 \u00b5mol\/L with DAPA\/SAXA (P &amp;lt; 0.05, Pre-Tx vs. Post-Tx). In DAPA, carbohydrate oxidation rates decreased from 1.1 \u00b1 0.1 to 0.7 \u00b1 0.1 mg\/kg\/min, whereas lipid oxidation rates increased from 0.6 \u00b1 0.1 to 0.8 \u00b1 0.1 mg\/kg\/min (P &amp;lt; 0.01). In DAPA\/SAXA, the shift in carbohydrate (1.1 \u00b1 0.1 to 0.9 \u00b1 0.1 mg\/kg\/min) and lipid (0.6 \u00b1 0.1 to 0.7 \u00b1 0.1 mg\/kg\/min) oxidation was attenuated (P &amp;lt; 0.05).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>The addition of SAXA to DAPA resulted in superior glycemic control compared with DAPA monotherapy partly because of increased glucose utilization and oxidation. Although the decrease in insulin\/glucagon ratio was prevented by SAXA, EGP paradoxical elevation persisted, indicating that other factors mediate EGP changes in response to SGLT2i-induced glucosuria.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc19-1993","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T02:12:41Z","timestamp":1595383961000},"page":"2519-2527","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":6,"title":["Clinical Parameters, Fuel Oxidation, and Glucose Kinetics in Patients With Type 2 Diabetes Treated With Dapagliflozin Plus Saxagliptin"],"prefix":"10.2337","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct02613897","registry":"10.18810\/clinical-trials-gov","type":"results"}],"author":[{"given":"Yuejuan","family":"Qin","sequence":"first","affiliation":[{"name":"Texas Diabetes Institute\u2013University Health System and UT Health San Antonio, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Adams","sequence":"additional","affiliation":[{"name":"Texas Diabetes Institute\u2013University Health System and UT Health San Antonio, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6215-9418","authenticated-orcid":false,"given":"Carolina","family":"Solis-Herrera","sequence":"additional","affiliation":[{"name":"Texas Diabetes Institute\u2013University Health System and UT Health San Antonio, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis","family":"Triplitt","sequence":"additional","affiliation":[{"name":"Texas Diabetes Institute\u2013University Health System and UT Health San Antonio, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8581-6273","authenticated-orcid":false,"given":"Ralph","family":"DeFronzo","sequence":"additional","affiliation":[{"name":"Texas Diabetes Institute\u2013University Health System and UT Health San Antonio, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-0208","authenticated-orcid":false,"given":"Eugenio","family":"Cersosimo","sequence":"additional","affiliation":[{"name":"Texas Diabetes Institute\u2013University Health System and UT Health San Antonio, San Antonio, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"2022031223552888100_B1","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1056\/NEJM199309303291401","article-title":"The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus","volume":"329","author":"Nathan","year":"1993","journal-title":"N Engl J Med"},{"key":"2022031223552888100_B2","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S0140-6736(98)07019-6","article-title":"Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)","volume":"352","author":"UK Prospective Diabetes Study (UKPDS) Group","year":"1998","journal-title":"Lancet"},{"key":"2022031223552888100_B3","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1056\/NEJMc1306652","article-title":"Achievement of goals in U.S. Diabetes Care, 1999-2010","volume":"369","author":"Ali","year":"2013","journal-title":"N Engl J Med"},{"key":"2022031223552888100_B4","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1007\/s00125-018-4729-5","article-title":"Management of hyperglycemia in type 2 diabetes, 2018. 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