{"doi":"10.1172/jci.insight.150074","title":"IL-6 receptor blockade does not slow β cell loss in new-onset type 1 diabetes","abstract":"BackgroundIL-6 receptor (IL-6R) signaling drives development of T cell populations important to type 1 diabetes pathogenesis. We evaluated whether blockade of IL-6R with monoclonal antibody tocilizumab would slow loss of residual β cell function in newly diagnosed type 1 diabetes patients.MethodsWe conducted a multicenter, randomized, placebo-controlled, double-blind trial with tocilizumab in new-onset type 1 diabetes. Participants were screened within 100 days of diagnosis. Eligible participants were randomized 2:1 to receive 7 monthly doses of tocilizumab or placebo. The primary outcome was the change from screening in the mean AUC of C-peptide collected during the first 2 hours of a mixed meal tolerance test at week 52 in pediatric participants (ages 6-17 years).ResultsThere was no statistical difference in the primary outcome between tocilizumab and placebo. Immunophenotyping showed reductions in downstream signaling of the IL-6R in T cells but no changes in CD4 memory subsets, Th17 cells, Tregs, or CD4+ T effector cell resistance to Treg suppression. A DC subset decreased during therapy but regressed to baseline once therapy stopped. Tocilizumab was well tolerated.ConclusionTocilizumab reduced T cell IL-6R signaling but did not modulate CD4+ T cell phenotypes or slow loss of residual β cell function in newly diagnosed individuals with type 1 diabetes.Trial RegistrationClinicalTrials.gov NCT02293837.FundingNIH National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute of Allergy and Infectious Diseases (NIAID) UM1AI109565, UL1TR000004 from NIH/National Center for Research Resources (NCRR) Clinical and Translational Science Award (CTSA), NIH/NIDDK P30DK036836, NIH/NIDDK U01DK103266, NIH/NIDDK U01DK103266, 1UL1TR000064 from NIH/NCRR CTSA, NIH/National Center for Advancing Translational Sciences (NCATS) UL1TR001878, UL1TR002537 from NIH/CTSA; National Health and Medical Research Council Practitioner Fellowship (APP1136735), NIH/NIDDK U01-DK085476, NIH/CTSA UL1-TR002494, Indiana Clinical and Translational Science Institute Award UL1TR002529, Vanderbilt Institute for Clinical and Translational Research UL1TR000445. NIH/NCATS UL1TR003142, NIH/CTSA program UL1-TR002494, Veteran Affairs Administration, and 1R01AI132774.","journal":"JCI Insight","year":2021,"id":155406,"datarank":2.154777581190305,"base_score":4.0943445622221,"endowment":4.0943445622221,"self_citation_contribution":0.6141516843333151,"citation_network_contribution":1.5406258968569897,"self_endowment_contribution":0.6141516843333151,"citer_contribution":1.5406258968569897,"corpus_percentile":null,"corpus_rank":null,"citation_count":59,"citer_count":47,"citers_with_citation_signal":41,"citers_with_endowment":41,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02293837"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":272838,"name":"Elisavet Serti","orcid":null,"position":1,"is_corresponding":false},{"id":539627,"name":"Katharina Lambert","orcid":"0000-0002-1998-0024","position":2,"is_corresponding":false},{"id":659096,"name":"Lia J. Weiner","orcid":null,"position":3,"is_corresponding":false},{"id":287334,"name":"Sai Kanaparthi","orcid":null,"position":4,"is_corresponding":false},{"id":658029,"name":"Sandra Lord","orcid":"0000-0003-3508-0402","position":5,"is_corresponding":false},{"id":336607,"name":"Stephen E. Gitelman","orcid":"0000-0003-4186-4107","position":6,"is_corresponding":false},{"id":71413,"name":"Darrell M. Wilson","orcid":"0000-0001-9589-6011","position":7,"is_corresponding":false},{"id":336606,"name":"Jason L. Gaglia","orcid":"0000-0003-2904-312X","position":8,"is_corresponding":false},{"id":658030,"name":"Kurt Griffin","orcid":"0000-0003-2374-0733","position":9,"is_corresponding":false},{"id":374833,"name":"William E. Russell","orcid":"0000-0001-7609-0434","position":10,"is_corresponding":false},{"id":462284,"name":"Philip Raskin","orcid":null,"position":11,"is_corresponding":false},{"id":513353,"name":"Antoinette Moran","orcid":"0000-0002-2694-5147","position":12,"is_corresponding":false},{"id":246571,"name":"Steven M. Willi","orcid":"0000-0002-4910-2425","position":13,"is_corresponding":false},{"id":384616,"name":"Eva Tsalikian","orcid":"0000-0003-3429-2796","position":14,"is_corresponding":false},{"id":513350,"name":"Linda A. DiMeglio","orcid":"0000-0002-8033-6078","position":15,"is_corresponding":false},{"id":230352,"name":"Kevan C. Herold","orcid":"0000-0003-1534-6613","position":16,"is_corresponding":false},{"id":216290,"name":"Wayne V. Moore","orcid":null,"position":17,"is_corresponding":false},{"id":234224,"name":"Robin Goland","orcid":null,"position":18,"is_corresponding":false},{"id":658031,"name":"Mark Harris","orcid":"0000-0002-0705-8913","position":19,"is_corresponding":false},{"id":658032,"name":"Maria E. Craig","orcid":"0000-0001-6004-576X","position":20,"is_corresponding":false},{"id":477239,"name":"Desmond A. Schatz","orcid":"0000-0003-3267-8265","position":21,"is_corresponding":false},{"id":336605,"name":"David A. Baidal","orcid":"0000-0001-7694-3265","position":22,"is_corresponding":false},{"id":787,"name":"Henry Rodriguez","orcid":"0000-0002-4593-4232","position":23,"is_corresponding":false},{"id":249040,"name":"Kristina M. Utzschneider","orcid":"0000-0002-4924-196X","position":24,"is_corresponding":false},{"id":658033,"name":"Hendrik J. Nel","orcid":"0000-0001-7029-1788","position":25,"is_corresponding":false},{"id":630330,"name":"Carol L. Soppe","orcid":"0000-0002-8538-6314","position":26,"is_corresponding":false},{"id":659097,"name":"Karen D. Boyle","orcid":null,"position":27,"is_corresponding":false},{"id":644646,"name":"Karen Cerosaletti","orcid":"0000-0002-7403-6239","position":28,"is_corresponding":false},{"id":462537,"name":"Lynette Keyes-Elstein","orcid":null,"position":29,"is_corresponding":false},{"id":308289,"name":"S. Alice Long","orcid":"0000-0002-0281-1240","position":30,"is_corresponding":false},{"id":456366,"name":"Ranjeny Thomas","orcid":"0000-0002-0518-8386","position":31,"is_corresponding":false},{"id":658034,"name":"James McNamara","orcid":"0000-0002-0995-6151","position":32,"is_corresponding":false},{"id":226226,"name":"Jane H. Buckner","orcid":"0000-0002-9005-1885","position":33,"is_corresponding":false},{"id":333914,"name":"Srinath Sanda","orcid":"0000-0002-6983-6864","position":34,"is_corresponding":false},{"id":659098,"name":"for the ITN058AI EXTEND Study Team","orcid":null,"position":35,"is_corresponding":false},{"id":71415,"name":"Carla J. Greenbaum","orcid":"0000-0003-4451-9800","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T23:44:03.750995Z","pmid":"34747368","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}