{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T23:50:00Z","timestamp":1773013800642,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004312","name":"Eli Lilly and Company","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004312","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate treatment\u2010emergent antidrug antibodies (TE ADA) in once\u2010weekly basal insulin efsitora\u2010treated participants with type 1 and type 2 diabetes mellitus (T1DM and T2DM) from 5 phase 3 clinical trials and their potential impact on pharmacokinetics, efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Serum samples were collected at baseline and throughout the studies. ADA were measured and characterised for their cross\u2010reactivity to native insulin or ability to neutralise efsitora or endogenous insulin. ADA impact on the pharmacokinetics, efficacy and safety of efsitora was evaluated by comparing the clearance of efsitora, glycated haemoglobin (HbA1c) change from baseline at the primary endpoint, and incidence of treatment\u2010emergent hypersensitivity reactions or injection site reactions by ADA status, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>About 0.6% and 3.0% of efsitora\u2010treated participants with T1DM (341) and T2DM (1861), respectively, developed TE ADA. Cross\u2010reactive antibodies to native insulin and neutralising antibodies against efsitora and native insulin were observed in 1.7%, 1.1% and 0.8% of efsitora\u2010treated participants with T2DM, respectively, but not in those with T1DM. Maximum ADA titres ranged from 1:40 to 1:81\u2009920, with a median of 1:80. The clearance of efsitora was similar between baseline ADA+ and ADA\u2212 groups. TE ADA status did not significantly affect HbA1c reduction or cause hypersensitivity or injection site reactions in efsitora\u2010treated participants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Efsitora caused an immunogenic response in up to 3.0% of participants with T1DM and T2DM. Descriptive analysis indicates that the immunogenicity of efsitora did not noticeably impact its pharmacokinetics, efficacy or safety. The molecular design of efsitora may contribute to its low immunogenicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70325","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T02:45:57Z","timestamp":1764902757000},"page":"1350-1358","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Low immunogenicity of insulin efsitora alfa in participants with type 1 and type 2 diabetes mellitus"],"prefix":"10.1111","volume":"28","author":[{"given":"Yun","family":"Wang","sequence":"first","affiliation":[{"name":"Lilly Research Laboratories Eli Lilly and Company, Lilly Corporate Center  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sihe","family":"Wang","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Eli Lilly and Company, Lilly Corporate Center  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Eli Lilly and Company, Lilly Corporate Center  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqi","family":"Li","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Eli Lilly and Company, Lilly Corporate Center  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5434-7905","authenticated-orcid":false,"given":"Jennifer","family":"Leohr","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Eli Lilly and Company, Lilly Corporate Center  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitoria","family":"Pires","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Eli Lilly and Company, Lilly Corporate Center  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle L.","family":"Katz","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Eli Lilly and Company, Lilly Corporate Center  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Child","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Eli Lilly and Company, Lilly Corporate Center  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0923-0542","authenticated-orcid":false,"given":"Robert J.","family":"Konrad","sequence":"additional","affiliation":[{"name":"Lilly Research Laboratories Eli Lilly and Company, Lilly Corporate Center  Indianapolis Indiana USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14956"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.122.001105"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/1744666X.2018.1468753"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/cts.2020.493"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2502796"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2403953"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)01044-X"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)01069-4"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01804-X"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15604"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2016.02.008"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2023.113575"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad532"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1267"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc08-1431"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000002356"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.5863\/1551-6776-21.1.85"},{"key":"e_1_2_10_19_1","unstructured":"FDA.Clinical immunogenicity considerations for biosimilar and interchangeable insulin products. 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