{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:10:20Z","timestamp":1791868220171,"version":"4.3.4"},"reference-count":50,"publisher":"Korean Diabetes Association","issue":"5","license":[{"start":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T00:00:00Z","timestamp":1765756800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004470","name":"Daewoong Pharmaceutical Co., Ltd","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004470","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>Background: The study evaluated the efficacy and safety of enavogliflozin, a novel, promising selective sodium-glucose cotransporter 2 inhibitor, as an add-on in adults with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin alone or combined with other antidiabetic drugs (OADs).Methods: The double-blind, placebo-controlled, multicenter trial was conducted in South Korea and Thailand. Individuals with glycosylated hemoglobin (HbA1c) \u22657.5% after \u22658-week treatment with background insulin alone or combined with \u22642 OADs were randomized to receive enavogliflozin 0.3 mg or placebo (&lt;i&gt;n&lt;\/i&gt;=120 each) for 24 weeks. The primary outcome was a change in HbA1c at week 24. Secondary outcomes included, among others, changes in body weight, blood pressure, and other measures of glycemic control. Adverse events (AEs) were investigated throughout the study (Clinical trial registration number: NCT05466643).Results: At week 24, the placebo-adjusted mean change in HbA1c from baseline in the enavogliflozin group was \u20130.9% (&lt;i&gt;P&lt;\/i&gt;&lt;0.001). Also, placebo-adjusted mean changes in fasting plasma glucose (\u201332.4 mg\/dL, &lt;i&gt;P&lt;\/i&gt;&lt;0.001), body weight (\u20131.3 kg, &lt;i&gt;P&lt;\/i&gt;&lt;0.001), and total daily dose of insulin (\u20131.3 units, &lt;i&gt;P&lt;\/i&gt;=0.010) at week 24 were statistically significant. In addition, a significant decrease in blood pressure and fasting C-peptide was observed in the enavogliflozin group, along with a significant increase in homeostasis model assessment of \u03b2-cell function, yet without a concomitant change in homeostasis model assessment of insulinresistance. No significant increase in treatment-related AEs was observed for enavogliflozin.Conclusion: Enavogliflozin 0.3 mg\/day is an efficacious and safe add-on treatment option in T2DM patients controlled inadequately with insulin alone or combined with OADs.<\/jats:p>","DOI":"10.4093\/dmj.2025.0477","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:48:59Z","timestamp":1765846139000},"page":"952-964","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and Safety of Enavogliflozin as Add-on in Adults with Type 2 Diabetes Mellitus Inadequately Controlled with Insulin or Insulin with Other Antidiabetic Drugs"],"prefix":"10.4093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8693-1038","authenticated-orcid":true,"given":"Jun Hwa","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Daejeon Eulji Medical Center, Eulji University, Daejeon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Wan","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang Beom","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parinya","family":"Chamnan","sequence":"additional","affiliation":[{"name":"Cardiometabolic Research Group, Department of Social Medicine, Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanitha","family":"Sirirak","sequence":"additional","affiliation":[{"name":"Department of Family Medicine and Preventive Medicine, Faculty of Medicine, Songklanagarind Hospital, Songkhla, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran","family":"Sony","sequence":"additional","affiliation":[{"name":"Department of Medicine, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarinya","family":"Sattanon","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Naresuan University Hospital, Phitsanulok, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Yong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Chosun University Hospital, Gwangju, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younghee","family":"Kim","sequence":"additional","affiliation":[{"name":"Daewoong Pharmaceutical Co., Ltd., Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung A","family":"Heo","sequence":"additional","affiliation":[{"name":"Daewoong Pharmaceutical Co., Ltd., Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Min","family":"Cho","sequence":"additional","affiliation":[{"name":"Daewoong Pharmaceutical Co., Ltd., Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Jin","family":"Nah","sequence":"additional","affiliation":[{"name":"Daewoong Pharmaceutical Co., Ltd., Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Hee","family":"Park","sequence":"additional","affiliation":[{"name":"Daewoong Pharmaceutical Co., Ltd., Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5001-963X","authenticated-orcid":true,"given":"Jae Hyeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2567","reference":[{"key":"ref1","volume-title":"","year":"2025","type":"book"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2024.0818","type":"journal-article"},{"key":"ref3","first-page":"S181","volume-title":"9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2025","year":"2025","type":"journal-article"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.2337\/dc25-s006","type":"journal-article"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.13539","type":"journal-article"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1186\/1746-1596-9-130","type":"journal-article"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2014.38.3.197","type":"journal-article"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.24.4.758","type":"journal-article"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006112","type":"journal-article"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2019.0208","type":"journal-article"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1504720","type":"journal-article"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1611925","type":"journal-article"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22066","type":"journal-article"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.172268","type":"journal-article"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2023.102816","type":"journal-article"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics12030268","type":"journal-article"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15348","type":"journal-article"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14061210","type":"journal-article"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15030942","type":"journal-article"},{"key":"ref20","first-page":"1865","type":"journal-article","volume-title":"Efficacy and safety of enavogliflozin, a novel SGLT2 inhibitor, in Korean people with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, placebo-controlled, phase III trial","author":"Kwak","year":"2023"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2022.0315","type":"journal-article"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2023.101440","type":"journal-article"},{"key":"ref23","first-page":"2096","type":"journal-article","volume-title":"Efficacy and safety of monotherapy with enavogliflozin in Korean patients with type 2 diabetes mellitus: results of a 12-week, multicentre, randomized, double-blind, placebo-controlled, phase 2 trial","author":"Yang","year":"2023"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.12634","type":"journal-article"},{"key":"ref25","first-page":"123","type":"journal-article","volume-title":"Efficacy and safety of gemigliptin as add-on therapy to insulin, with or without metformin, in patients with type 2 diabetes mellitus (ZEUS II study)","author":"Cho","year":"2020"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-156-6-201203200-00003","type":"journal-article"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12187","type":"journal-article"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-3055","type":"journal-article"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12503","type":"journal-article"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1237","type":"journal-article"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-0315","type":"journal-article"},{"key":"ref32","first-page":"1207","type":"journal-article","volume-title":"Efficacy and safety of ipragliflozin as add-on therapy to insulin in Japanese patients with type 2 diabetes mellitus (IOLITE): a multi-centre, randomized, placebo-controlled, double-blind study","author":"Ishihara","year":"2016"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.14740\/jocmr2741w","type":"journal-article"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-016-0407-4","type":"journal-article"},{"key":"ref35","first-page":"562","type":"journal-article","volume-title":"Efficacy and safety of dapagliflozin over 1 year as add-on to insulin therapy in Japanese patients with type 2 diabetes: the DAISY (Dapagliflozin Added to patients under InSulin therapY) trial","author":"Araki","year":"2017"},{"key":"ref36","first-page":"1397","type":"journal-article","volume-title":"Efficacy and safety of tofogliflozin in Japanese patients with type 2 diabetes mellitus with inadequate glycaemic control on insulin therapy (J-STEP\/INS): results of a 16-week randomized, double-blind, placebo-controlled multicentre trial","author":"Terauchi","year":"2017"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1080\/03007995.2018.1441816","type":"journal-article"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13909","type":"journal-article"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.27.6.1487","type":"journal-article"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1038\/srep44865","type":"journal-article"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.12453","type":"journal-article"},{"key":"ref42","first-page":"1364","type":"journal-article","volume-title":"Management of hyperglycemia 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)","author":"Inzucchi","year":"2012"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-1596","type":"journal-article"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00390.2012","type":"journal-article"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2025.0220","type":"journal-article"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2009.07.090","type":"journal-article"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.26.2.510","type":"journal-article"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2013.12.052","type":"journal-article"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.1111\/dme.12624","type":"journal-article"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12327","type":"journal-article"}],"container-title":["Diabetes &amp; Metabolism Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2025-0477.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2025.0477","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2025-0477.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T07:32:30Z","timestamp":1788939150000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2025.0477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,9]]}},"URL":"https:\/\/doi.org\/10.4093\/dmj.2025.0477","relation":{},"ISSN":["2233-6079","2233-6087"],"issn-type":[{"value":"2233-6079","type":"print"},{"value":"2233-6087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]},"assertion":[{"value":"2025-05-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-15","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}