{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:02:40Z","timestamp":1792098160543,"version":"4.4.0"},"reference-count":8,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"vor","delay-in-days":336,"URL":"http:\/\/www.diabetesjournals.org\/site\/license"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>Insulin adjustments to maintain glycemic control in individuals with type 1 diabetes often lead to wide glucose fluctuations, hypoglycemia, and increased body weight. Dapagliflozin, an insulin-independent sodium\u2013glucose cotransporter 2 (SGLT2) inhibitor, increases glucosuria and reduces hyperglycemia in individuals with type 2 diabetes. The primary objective of this study was to assess short-term safety of dapagliflozin in combination with insulin; secondary objectives included pharmacokinetic, pharmacodynamic, and efficacy parameters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>A 2-week, dose-ranging, randomized, double-blind, placebo-controlled proof-of-concept study randomly assigned 70 adults with type 1 diabetes (HbA1c 7\u201310%), who were receiving treatment with stable doses of insulin, to one of four dapagliflozin doses (1, 2.5, 5, or 10 mg) or placebo. The insulin dose was not proactively reduced at randomization but could be adjusted for safety reasons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Sixty-two patients (88.6%) completed the study. Any hypoglycemia was common across all treatments (60.0\u201392.3%); one major event of hypoglycemia occurred with dapagliflozin 10 mg. No diabetic ketoacidosis occurred. Pharmacokinetic parameters were similar to those observed in patients with type 2 diabetes. Glucosuria increased by 88 g\/24 h (95% CI 55 to 121) with dapagliflozin 10 mg and decreased by \u221221.5 g\/24 h (95% CI \u221253.9 to 11.0) with placebo. Changes from baseline with dapagliflozin 10 mg by day 7 were as follows: \u22122.29 mmol\/L (95% CI \u22123.71 to \u22120.87 [\u221241.3 mg\/dL; 95% CI \u221266.9 to \u221215.7]) for 24-h daily average blood glucose; \u22123.77 mmol\/L (95% CI \u22126.09 to \u22121.45 [\u221263.1 mg\/dL; 95% CI \u2212111.5 to \u221214.8]) for mean amplitude of glycemic excursion; and \u221216.2% (95% CI \u221229.4 to \u22120.5) for mean percent change in total daily insulin dose. Corresponding changes with placebo were as follows: \u22121.13 mmol\/L (95% CI \u22123.63 to 1.37), \u22120.45 mmol\/L (95% CI \u22124.98 to 4.08), and 1.7% (95% CI \u221222.8 to 33.9), respectively. However, for every efficacy parameter, the 95% CIs for all dapagliflozin doses overlapped those for placebo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>This exploratory study of dapagliflozin in adults with type 1 diabetes demonstrated acceptable short-term tolerability and expected pharmacokinetic profiles and increases in urinary glucose excretion. Within the dapagliflozin groups, dose-related reductions in 24-h glucose, glycemic variability, and insulin dose were suggested, which provide hope that SGLT2 inhibition may prove in larger randomized controlled trials to be efficacious in reducing hyperglycemia in type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc13-2955","type":"journal-article","created":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:45:15Z","timestamp":1412124315000},"page":"412-419","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":177,"title":["Exploring the Potential of the SGLT2 Inhibitor Dapagliflozin in Type 1 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Pilot Study"],"prefix":"10.2337","volume":"38","author":[{"given":"Robert R.","family":"Henry","sequence":"first","affiliation":[{"name":"Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA"},{"name":"University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Rosenstock","sequence":"additional","affiliation":[{"name":"Dallas Diabetes and Endocrine Center at Medical City, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Edelman","sequence":"additional","affiliation":[{"name":"Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA"},{"name":"University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunder","family":"Mudaliar","sequence":"additional","affiliation":[{"name":"Center for Metabolic Research, VA San Diego Healthcare System, San Diego, CA"},{"name":"University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandros-Georgios","family":"Chalamandaris","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Braine-l'Alleud, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreeneeranj","family":"Kasichayanula","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Princeton, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyson","family":"Bogle","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Princeton, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayyar","family":"Iqbal","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Princeton, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"List","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Princeton, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Griffen","sequence":"additional","affiliation":[{"name":"Bristol-Myers Squibb, Princeton, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2014,9,30]]},"reference":[{"key":"2022031301340550500_B1","doi-asserted-by":"crossref","first-page":"3411","DOI":"10.1210\/jc.2013-1589","article-title":"Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D exchange clinic registry","volume":"98","author":"Weinstock","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"2022031301340550500_B2","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/j.1463-1326.2006.00686.x","article-title":"Insulin-associated weight gain in diabetes\u2014causes, effects and coping strategies","volume":"9","author":"Russell-Jones","year":"2007","journal-title":"Diabetes Obes Metab"},{"key":"2022031301340550500_B3","doi-asserted-by":"crossref","first-page":"707","DOI":"10.2337\/dc06-1982","article-title":"Insulin resistance, the metabolic syndrome, and complication risk in type 1 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glucose and renal hemodynamcis during rapid hypertonic glucose infusion in normal and diabetic subjects","volume":"28","author":"Mogensen","year":"1971","journal-title":"Scand J Clin Lab Invest"},{"key":"2022031301340550500_B7","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1111\/j.1463-1326.2011.01359.x","article-title":"Pharmacokinetics and pharmacodynamics of dapagliflozin, a novel selective inhibitor of sodium-glucose co-transporter type 2, in Japanese subjects without and with type 2 diabetes mellitus","volume":"13","author":"Kasichayanula","year":"2011","journal-title":"Diabetes Obes Metab"},{"key":"2022031301340550500_B8","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/clpt.2008.250","article-title":"Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus","volume":"85","author":"Komoroski","year":"2009","journal-title":"Clin Pharmacol Ther"}],"container-title":["Diabetes 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