{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T10:20:00Z","timestamp":1790850000194,"version":"4.1.0"},"reference-count":24,"publisher":"The Endocrine Society","issue":"1","license":[{"start":{"date-parts":[[2023,7,22]],"date-time":"2023-07-22T00:00:00Z","timestamp":1689984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"AstraZeneca Pharmaceuticals"},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["RO1-DK107680-05"],"award-info":[{"award-number":["RO1-DK107680-05"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>This study addresses the development of a new glucoregulatory mechanism in type 2 diabetes (T2D) patients treated with SGLT-2 inhibitors, which is independent of glucose, insulin and glucagon. The data suggest the presence of a potential trigger factor (s) arising in the kidney that stimulates endogenous glucose production (EGP) during sustained glycosuria.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To investigate effects of SGLT-2 inhibitor therapy together with GLP-1 receptor agonist on EGP and glucose kinetics in patients with T2D. Our hypothesis was that increased EGP in response to SGLT2i-induced glycosuria persists for a long period and is not abolished by GLP-1 RA stimulation of insulin secretion and glucagon suppression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Seventy-five patients received a 5-hour dual-tracer oral glucose tolerance test (OGTT) (intravenous 3-(3H)-glucose oral (1-14C)-glucose): (1) before\/after 1 of dapagliflozin (DAPA); exenatide (EXE), or both, DAPA\/EXE (acute study), and (2) after 1 and 4 months of therapy with each drug.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the acute study, during the OGTT plasma glucose (PG) elevation was lower in EXE (\u0394 = 42 \u00b1 1 mg\/dL) than DAPA (\u0394 = 72 \u00b1 3), and lower in DAPA\/EXE (\u0394 = 11 \u00b1 3) than EXE and DAPA. EGP decrease was lower in DAPA (\u0394 = \u22120.65 \u00b1 0.03 mg\/kg\/min) than EXE (\u0394 = \u22120.96 \u00b1 0.07); in DAPA\/EXE (\u0394 = \u22120.84 \u00b1 0.05) it was lower than EXE, higher than DAPA. At 1 month, similar PG elevations (EXE, \u0394 = 26 \u00b1 1 mg\/dL; DAPA, \u0394 = 62 \u00b1 2, DAPA\/EXE, \u0394 = 27 \u00b1 1) and EGP decreases (DAPA, \u0394 = \u22120.60 \u00b1 0.05 mg\/kg\/min; EXE, \u0394 = \u22120.77 \u00b1 0.04; DAPA\/EXE, \u0394 = \u22120.72 \u00b1 0.03) were observed. At 4 months, PG elevations (EXE, \u0394 = 55 \u00b1 2 mg\/dL; DAPA, \u0394 = 65 \u00b1 6; DAPA\/EXE, \u0394 = 46 \u00b1 2) and lower EGP decrease in DAPA (\u0394 = \u22120.66 \u00b1 0.04 mg\/kg\/min) vs EXE (\u0394 = \u22120.84 \u00b1 0.05) were also comparable; in DAPA\/EXE (\u0394 = \u22120.65 \u00b1 0.03) it was equal to DAPA and lower than EXE. Changes in plasma insulin\/glucagon could not explain higher EGP in DAPA\/EXE vs EXE mg\/kg\/min.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our findings provide strong evidence for the emergence of a new long-lasting, glucose-independent, insulin\/glucagon-independent, glucoregulatory mechanism via which SGLT2i-induced glycosuria stimulates EGP in patients with T2D. SGLT2i plus GLP-1 receptor agonist combination therapy is accompanied by superior glycemic control vs monotherapy.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgad438","type":"journal-article","created":{"date-parts":[[2023,7,23]],"date-time":"2023-07-23T00:06:56Z","timestamp":1690070816000},"page":"161-170","source":"Crossref","is-referenced-by-count":11,"title":["Emergence of a New Glucoregulatory Mechanism for Glycemic Control With Dapagliflozin\/Exenatide Therapy in Type 2 Diabetes"],"prefix":"10.1210","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-0208","authenticated-orcid":false,"given":"Eugenio","family":"Cersosimo","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, University Health System , San Antonio, TX 78229 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Institute, University Health System , San Antonio, TX 78229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Adams","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, University Health System , San Antonio, TX 78229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Hansis-Diarte","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, University Health System , San Antonio, TX 78229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Diabetes, University of Texas Health Science Center and Texas Diabetes Institute, 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