{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T23:58:56Z","timestamp":1791849536930,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,8,29]],"date-time":"2013-08-29T00:00:00Z","timestamp":1377734400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Dapagliflozin, a selective inhibitor of sodium\u2010glucose cotransporter 2 (\n                      <jats:styled-content style=\"fixed-case\">SGLT2<\/jats:styled-content>\n                      ), has been shown to improve glycaemic control, stabilize insulin dosing and mitigate insulin\u2010associated weight gain over 48\u2009weeks in patients whose type 2 diabetes mellitus (\n                      <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                      ) was inadequately controlled despite high doses of insulin. Here the efficacy and safety of dapagliflozin therapy after a total of 104\u2009weeks are evaluated in this population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This was a 24\u2010week, randomized, placebo\u2010controlled, double\u2010blinded, multicentre trial followed by two site\u2010 and patient\u2010blinded extension periods of 24 and 56\u2009weeks (NCT00673231), respectively. A total of 808 patients, whose\n                      <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                      was inadequately controlled on insulin \u226530\n                      <jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\n                      \/day, with or without up to two oral antidiabetic drugs, were randomly assigned to receive placebo or 2.5, 5 or 10\u2009mg\/day of dapagliflozin for 104\u2009weeks. At 48\u2009weeks, patients on dapagliflozin 5\u2009mg were switched to 10\u2009mg. Outcomes over 104\u2009weeks included change from baseline in\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      , insulin dose and body weight; analyses used observed cases and included data after insulin up\u2010titration. Adverse events (\n                      <jats:styled-content style=\"fixed-case\">AEs<\/jats:styled-content>\n                      ) were evaluated throughout 104\u2009weeks.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five hundred and thirteen patients (63.6%) completed the study. Mean\n                      <jats:styled-content style=\"fixed-case\">HbA1c<\/jats:styled-content>\n                      changes from baseline at 104\u2009weeks were \u22120.4% in the placebo group and \u22120.6 to \u22120.8% in the dapagliflozin groups. In the placebo group, mean insulin dose increased by 18.3\n                      <jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\n                      \/day and weight increased by 1.8\u2009kg at 104\u2009weeks, whereas in the dapagliflozin groups, insulin dose was stable and weight decreased by 0.9\u20131.4\u2009kg.\n                      <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>\n                      s, including hypoglycaemia, were balanced across groups. Proportions of patients with events suggestive of genital infection and of urinary tract infection (\n                      <jats:styled-content style=\"fixed-case\">UTI<\/jats:styled-content>\n                      ) were higher with dapagliflozin versus placebo (genital infection 7.4\u201314.3% vs. 3.0%;\n                      <jats:styled-content style=\"fixed-case\">UTI<\/jats:styled-content>\n                      8.4\u201313.8% vs. 5.6%) but most occurred in the first 24\u2009weeks and most were single episodes that responded to routine management.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Dapagliflozin improved glycaemic control, stabilized insulin dosing and reduced weight without increasing major hypoglycaemic episodes over 104\u2009weeks in patients whose\n                      <jats:styled-content style=\"fixed-case\">T2DM<\/jats:styled-content>\n                      was inadequately controlled on insulin. However, rates of genital infection and of\n                      <jats:styled-content style=\"fixed-case\">UTI<\/jats:styled-content>\n                      were elevated with dapagliflozin therapy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.12187","type":"journal-article","created":{"date-parts":[[2013,8,2]],"date-time":"2013-08-02T05:45:36Z","timestamp":1375422336000},"page":"124-136","source":"Crossref","is-referenced-by-count":240,"title":["Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years"],"prefix":"10.1111","volume":"16","author":[{"given":"J. P. 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