{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T08:12:07Z","timestamp":1778487127887,"version":"3.51.4"},"reference-count":40,"publisher":"Korean Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A2C2004570"],"award-info":[{"award-number":["2022R1A2C2004570"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Novo Nordisk"}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>Background: We aimed to confirm that once-daily insulin degludec\/insulin aspart (IDegAsp) is superior to basal insulin therapy in participants with type 2 diabetes mellitus (T2DM) exhibiting signs of overbasalization. Additionally, we analyzed incretin profiles in relation to the benefits of IDegAsp, providing insights into the underlying mechanisms.Methods: A prospective study was conducted in participants receiving basal insulin therapy, with a fasting plasma glucose (FPG) level lower than predicted from their glycosylated hemoglobin (HbA1c). Participants were randomly assigned to either IDegAsp or insulin glargine (IGlar) in a 1:1 ratio. After 20 weeks of treatment, the insulins were switched in a crossover design. The primary endpoint was the change in HbA1c from baseline. Incretin profiles, hypoglycemic events, and continuous glucose monitoring (CGM) were also analyzed (Trial registration: www.cris.nih.go.kr; KCT0004597).Results: The study included 55 participants (male 40%, mean age 65 years, FPG 103 mg\/dL, and HbA1c 8.3%). HbA1c significantly decreased to 7.8%\u00b10.8% with IDegAsp, compared to 8.0%\u00b10.7% with IGlar. The mean estimated treatment difference of changes was \u20130.21% points (95% confidence interval, \u20130.39 to \u20130.02; &lt;i&gt;P&lt;\/i&gt;=0.031), favoring IDegAsp. Hypoglycemic events were comparable. CGM demonstrated significantly lower glucose measures during the daytime with IDegAsp compared to IGlar, and vice versa at dawn. The HbA1c benefit of IDegAsp over IGlar was associated with a low glucagon-like peptide-1 (GLP-1) ratio at 30 minutes relative to baseline (r=0.301, &lt;i&gt;P&lt;\/i&gt;=0.040), while not with glucose-dependent insulinotropic polypeptide.Conclusion: The greater reduction in HbA1c achieved with IDegAsp compared to IGlar in individuals with T2DM was associated with an impaired GLP-1 response, facilitating personalized insulin therapy.<\/jats:p>","DOI":"10.4093\/dmj.2024.0741","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T05:16:17Z","timestamp":1755148577000},"page":"552-564","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glycemic Benefit of Insulin Degludec\/Insulin Aspart Compared to Basal Insulin in Type 2 Diabetes Mellitus Associated with Impaired Glucagon-Like Peptide-1 Response: A Randomized Crossover Trial"],"prefix":"10.4093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6186-2937","authenticated-orcid":true,"given":"Han Na","family":"Jang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0455-9154","authenticated-orcid":true,"given":"Eun Shil","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye Seul","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Ok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Myoung-jin","family":"Jang","sequence":"additional","affiliation":[{"name":"Medical Research Collaborating Center, Seoul National University Hospital, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Mari","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, National Research Council, Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Heon","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyong Soo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hak Chul","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0221-7049","authenticated-orcid":true,"given":"Hye Seung","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2567","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-s301"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-5491.1988.tb00938.x"},{"key":"ref3","first-page":"S158","volume-title":"9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2024","year":"2024"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2023.0282"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13518"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-014-1614-x"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-2908"},{"key":"ref8","first-page":"669","volume-title":"A new-generation ultra-long-acting basal insulin with a bolus boost compared with insulin glargine in insulin-naive people with type 2 diabetes: a randomized, controlled trial","author":"Heise","year":"2011"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12097"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0163350"},{"key":"ref11","first-page":"382","volume-title":"Favorable glycemic control with once-daily insulin degludec\/insulin aspart after changing from basal insulin in adults with type 2 diabetes","author":"Jang","year":"2019"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13634"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-023-05956-x"},{"key":"ref14","first-page":"42","volume-title":"Continuous glucose monitoring and metrics for clinical trials: an international consensus statement","author":"Battelino","year":"2023"},{"key":"ref15","volume-title":"Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus (2023)"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-2380"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-0545"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-022-02212-3"},{"key":"ref19","first-page":"1","volume-title":"Safety of insulin degludec\/insulin aspart in patients with diabetes mellitus over a period of 1 year during routine clinical care in India: SMART (Study of Management of Diabetes with RyzodegTM Treatment)","author":"Kesavadev","year":"2021"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13125"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1177\/193229681300700524"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12098"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(15)00482-9"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-002-0878-6"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0893"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-022-05796-1"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.2337\/db13-1757"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2019.0093"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1186\/s12902-024-01566-9"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-0366"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.8.3717"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-00194"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2013.10.008"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1044030"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1124"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.2337\/db14-1751"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-012-2484-6"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.93306"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.2337\/dc16-0691"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2012.01638.x"}],"container-title":["Diabetes &amp; Metabolism Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2024-0741.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2024.0741","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2024-0741.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T07:58:08Z","timestamp":1778486288000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2024.0741"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,1]]},"references-count":40,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"URL":"https:\/\/doi.org\/10.4093\/dmj.2024.0741","relation":{},"ISSN":["2233-6079","2233-6087"],"issn-type":[{"value":"2233-6079","type":"print"},{"value":"2233-6087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,1]]},"assertion":[{"value":"2024-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-14","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-01","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}