{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:08:50Z","timestamp":1773014930591,"version":"3.50.1"},"reference-count":18,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the immunogenicity, efficacy, and safety of a biosimilar insulin glulisine candidate (T\u2010Glu) compared to the reference product (R\u2010Glu) in patients with type 1 diabetes mellitus (T1DM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>In this phase III, randomised, open\u2010label trial, adult patients with T1DM received either T\u2010Glu or R\u2010Glu by prefilled pens as their bolus insulin for 26\u2009weeks. The primary outcome was the proportion of patients with an immune response at Week 26. Secondary endpoints included changes in glycaemia control parameters, insulin dose stability, treatment satisfaction, and other immunogenicity and safety outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      By Week 26, the immune response persisted in 16% of patients in the T\u2010Glu group and 24% in the R\u2010Glu group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05), confirming similar immunogenicity. HbA1c reduction at Week 26 compared to baseline was similar between groups, with a mean change of 0.53%\u2009\u00b1\u20091.19% in the T\u2010Glu group and 0.38%\u2009\u00b1\u20091.46% in the R\u2010Glu group (mean difference: \u22120.15%, 95% CI: \u22120.50 to 0.20), demonstrating non\u2010inferiority (according to a predefined margin of 0.4%). Fasting plasma glucose levels and the seven\u2010point glucose profile showed no significant differences between groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). Insulin dose remained stable throughout the study, and treatment satisfaction scores improved comparably in both groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&gt;\u20090.05). The total number of AEs was similar, and hypoglycaemia was more frequent in the R\u2010Glu group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), with no new safety concerns identified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>T\u2010Glu demonstrated similar immunogenicity, efficacy, and safety to R\u2010Glu in adults with T1DM, supporting its use as a biosimilar insulin glulisine.<\/jats:p>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\/\">ClinicalTrials.gov<\/jats:ext-link>\n                      : NCT07070752.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70360","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T04:02:07Z","timestamp":1765339327000},"page":"1791-1799","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunogenicity, efficacy and safety of a biosimilar insulin glulisine compared with originator in adults with type 1 diabetes mellitus: A phase\n                    <scp>III<\/scp>\n                    randomised clinical trial"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4594-6097","authenticated-orcid":false,"given":"Roman","family":"Drai","sequence":"first","affiliation":[{"name":"R&amp;D Center GEROPHARM  Saint Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6581-4521","authenticated-orcid":false,"given":"Gagik","family":"Galstyan","sequence":"additional","affiliation":[{"name":"Endocrinology Research Center  Moscow Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1547-0123","authenticated-orcid":false,"given":"Tatiana","family":"Karonova","sequence":"additional","affiliation":[{"name":"Almazov National Medical Research Centre  Saint Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4341-2884","authenticated-orcid":false,"given":"Ekaterina","family":"Protsenko","sequence":"additional","affiliation":[{"name":"R&amp;D Center GEROPHARM  Saint Petersburg Russia"},{"name":"Public Health Sciences ITMO University  Saint Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-6722","authenticated-orcid":false,"given":"Tatyana","family":"Parfenova","sequence":"additional","affiliation":[{"name":"Prof. V.F. Voino\u2010Yasenetsky Krasnoyarsk State Medical University  Krasnoyarsk Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3178-3581","authenticated-orcid":false,"given":"Anna","family":"Arefeva","sequence":"additional","affiliation":[{"name":"R&amp;D Center GEROPHARM  Saint Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3655-1707","authenticated-orcid":false,"given":"Iuliia","family":"Matvienko","sequence":"additional","affiliation":[{"name":"R&amp;D Center GEROPHARM  Saint Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3875-2024","authenticated-orcid":false,"given":"Dmitrii","family":"Iliushchenko","sequence":"additional","affiliation":[{"name":"R&amp;D Center GEROPHARM  Saint Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-0608","authenticated-orcid":false,"given":"Igor","family":"Makarenko","sequence":"additional","affiliation":[{"name":"R&amp;D Center GEROPHARM  Saint Petersburg Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"International Diabetes Federation.Diabetes Atlas. 10th ed. 2021. Accessed March 28 2025https:\/\/diabetesatlas.org\/atlas-presentation"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc23\u2010S009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14713"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010200847010\u201000002"},{"issue":"4","key":"e_1_2_9_6_1","article-title":"Biosimilar cost savings in the United States: initial experience and future potential","volume":"7","author":"Mulcahy AW","year":"2018","journal-title":"Rand Health Q"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S378813"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/20016689.2022"},{"key":"e_1_2_9_9_1","unstructured":"The Eurasian Economic Union.Resolution No. 89 of November 3 2016 On Approval of the Rules for Conduct of Studies of Biological medicines in the Eurasian Economic Union Chapter 15.7 Preclinical and Clinical Development of Bioanalogue (Biosimilar) Medicinal Products Containing Recombinant Insulin and Insulin Analogues. EMA. European Medical Agency. Guideline on Nonclinical and Clinical Development of Similar Biological Medicinal Products Containing Recombinant Human Insulin and Insulin Analogues; 2015. (EMEA\/CHMP\/BMWP\/32775\/2005 Rev. 1). Accessed March 28 2025https:\/\/www.ema.europa.eu\/en\/documents\/scientific\u2010guideline\/guideline\u2010non\u2010clinical\u2010and\u2010clinical\u2010development\u2010similar\u2010biological\u2010medicinal\u2010products\u2010containing\u2010recombinant\u2010human\u2010insulin\u2010and\u2010insulin\u2010analogues\u2010revision\u20101_en.pdf"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.1401"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26041730"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.14341\/DM12802"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12496"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.2217\/cer\u20102019\u20100136"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1214\/aos\/1013699998.full"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16320"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40259\u2010022\u201000554\u20106"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2019.0382"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/dia.2017.0117"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.70360","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/full-xml\/10.1111\/dom.70360","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.70360","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:00:54Z","timestamp":1773010854000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.70360"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,9]]},"references-count":18,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1111\/dom.70360"],"URL":"https:\/\/doi.org\/10.1111\/dom.70360","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.70360\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v1\/review5","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v1\/review4","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v2\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.70360\/v2\/decision1","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,9]]},"assertion":[{"value":"2025-09-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}