{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:35:09Z","timestamp":1777386909485,"version":"3.51.4"},"reference-count":28,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"vor","delay-in-days":3093,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,4,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE<\/jats:title>\n                  <jats:p>The requirement to inject current basal insulin analogs at a fixed time each day may complicate adherence and compromise glycemic control. This trial evaluated the efficacy and safety of varying the daily injection time of insulin degludec (IDeg), an ultra-long-acting basal insulin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                  <jats:p>This 26-week, open-label, treat-to-target trial enrolled adults (\u226518 years) with type 2 diabetes who were either insulin na\u00efve and receiving oral antidiabetic drugs (OADs) (HbA1c = 7\u201311%) or previously on basal insulin \u00b1 OAD(s) (HbA1c = 7\u201310%). Participants were randomized to 1) once-daily (OD) IDeg in a prespecified dosing schedule, creating 8\u201340-h intervals between injections (IDeg OD Flex; n = 229); 2) once-daily IDeg at the main evening meal (IDeg OD; n = 228); or 3) once-daily insulin glargine at the same time each day (IGlar OD; n = 230). The primary outcome was noninferiority of IDeg OD Flex to IGlar OD in HbA1c reduction after 26 weeks.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>After 26 weeks, IDeg OD Flex, IDeg OD, and IGlar OD improved HbA1c by 1.28, 1.07, and 1.26% points, respectively (estimated treatment difference [IDeg OD Flex \u2212 IGlar OD]: 0.04% points [\u20130.12 to 0.20], confirming noninferiority). No statistically significant differences in overall or nocturnal hypoglycemia were found between IDeg OD Flex and IGlar OD. Comparable glycemic control and rates of hypoglycemia were seen with IDeg OD Flex and IDeg OD. Adverse event profiles were similar across groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>The use of extreme dosing intervals of 8\u201340 h demonstrates that the daily injection time of IDeg can be varied without compromising glycemic control or safety.<\/jats:p>\n               <\/jats:sec>","DOI":"10.2337\/dc12-1668","type":"journal-article","created":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T02:37:02Z","timestamp":1358908622000},"page":"858-864","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":190,"title":["The Efficacy and Safety of Insulin Degludec Given in Variable Once-Daily Dosing Intervals Compared With Insulin Glargine and Insulin Degludec Dosed at the Same Time Daily"],"prefix":"10.2337","volume":"36","author":[{"given":"Luigi","family":"Meneghini","sequence":"first","affiliation":[{"name":"University of Miami Miller School of Medicine, Miami, Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen L.","family":"Atkin","sequence":"additional","affiliation":[{"name":"Michael White Diabetes Centre, Hull York Medical School, Hull, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen C.L.","family":"Gough","sequence":"additional","affiliation":[{"name":"Oxford Centre for Diabetes, Endocrinology, and Metabolism, and NIHR Oxford Biomedical Research Centre, Churchill Hospital, Oxford, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itamar","family":"Raz","sequence":"additional","affiliation":[{"name":"Diabetes Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence","family":"Blonde","sequence":"additional","affiliation":[{"name":"Ochsner Diabetes Research Unit, Department of Endocrinology, Ochsner Medical Center, New Orleans, Louisiana"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Shestakova","sequence":"additional","affiliation":[{"name":"Endocrinology Research Center, Moscow, Russian Federation"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Bain","sequence":"additional","affiliation":[{"name":"Abertawe Bro Morgannwg University Health Board, Singleton Hospital, Swansea, U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thue","family":"Johansen","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamilla","family":"Begtrup","sequence":"additional","affiliation":[{"name":"Novo Nordisk A\/S, S\u00f8borg, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K\u00e5re I.","family":"Birkeland","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Oslo University Hospital, and Faculty of Medicine, University of Oslo, Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the NN1250-3668 (BEGIN FLEX) Trial Investigators","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","published-online":{"date-parts":[[2013,3,14]]},"reference":[{"key":"2022031302024008500_B1","volume-title":"Diabetes Atlas","author":"International Diabetes Federation","year":"2011"},{"key":"2022031302024008500_B2","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2337\/dc08-9025","article-title":"Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"32","author":"Nathan","year":"2009","journal-title":"Diabetes Care"},{"key":"2022031302024008500_B3","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-012-2534-0","article-title":"Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)","volume":"55","author":"Inzucchi","year":"2012","journal-title":"Diabetologia"},{"key":"2022031302024008500_B4","doi-asserted-by":"crossref","first-page":"540","DOI":"10.4158\/EP.15.6.540","article-title":"Statement by an American Association of Clinical Endocrinologists\/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control","volume":"15","author":"Rodbard","year":"2009","journal-title":"Endocr Pract"},{"key":"2022031302024008500_B5","unstructured":"Lantus. European Public Assessment Report, Annex I: summary of product characteristics [Internet]. Available from http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/000284\/WC500036082.pdf. Accessed 17 October 2011"},{"key":"2022031302024008500_B6","unstructured":"Levemir. 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