Evidence map›Paper›PMID 34747368›Full record

Trial reportJCI insight2021

IL-6 receptor blockade does not slow β cell loss in new-onset type 1 diabetes.

Carla J Greenbaum, Elisavet Serti, Katharina Lambert, Lia J Weiner, Sai Kanaparthi, Sandra Lord, Stephen E Gitelman, Darrell M Wilson, Jason L Gaglia, Kurt J Griffin and 26 more

Registry-linked trialOpen access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02293837 (Preserving Beta-Cell Function With Tocilizumab in New-onset Type 1 Diabetes), which is not on this map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
6.4field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02293837 phase2completednot on this map

Preserving Beta-Cell Function With Tocilizumab in New-onset Type 1 Diabetes (ITN058AI)

TypeinterventionalSponsorNational Institute of Allergy and Infectious Diseases (NIAID)Ran2015 to 2020Enrolled136ConditionsType 1 Diabetes Mellitus, New-onset Type 1 Diabetes Mellitus, T1DM, T1DArmsTocilizumab (TCZ), Placebo, Standard of Care
3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Frontiers in endocrinology · 2023
    Trial
  4. Trial
  5. Article
  6. Type 1 Diabetes Mellitus Pathogenesis: Mechanisms, Early Diagnostic Strategies, and Emerging Therapeutic Approaches.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
  7. New and emerging therapies in type 1 diabetes mellitus.The Journal of clinical investigation · 2026
    Review
  8. Article
  9. Review
  10. Article
  11. Are We Ready With Prevention for Type 1 Diabetes?Diabetes/metabolism research and reviews · 2025
    Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

36 authors at 20 institutions in 2 countries.

Carla J GreenbaumCenter for Interventional Immunology and Diabetes Program, Benaroya Research Institute, Seattle, Washington, USA.
Elisavet SertiImmune Tolerance Network, Seattle, Washington, USA.
Katharina LambertCenter for Interventional Immunology and Diabetes Program, Benaroya Research Institute, Seattle, Washington, USA.
Lia J WeinerRho, Inc, Durham, North Carolina, USA.
Sai KanaparthiImmune Tolerance Network, Seattle, Washington, USA.
Sandra LordCenter for Interventional Immunology and Diabetes Program, Benaroya Research Institute, Seattle, Washington, USA.
Stephen E GitelmanUniversity of California, San Francisco, San Francisco, California, USA.
Darrell M WilsonStanford University, Stanford, California, USA.
Jason L GagliaJoslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
Kurt J GriffinSanford Health, San Jose, California, USA.
William E RussellVanderbilt University, Nashville, Tennessee, USA.
Philip RaskinUniversity of Texas, Southwestern, Dallas, Texas, USA.
Antoinette MoranUniversity of Minnesota, Minneapolis, Minnesota, USA.
Steven M WilliChildren's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Eva TsalikianUniversity of Iowa, Iowa City, Iowa, USA.
Linda A DiMeglioRiley Children's Hospital, Indiana University, Indianapolis, Indiana, USA.
Kevan C HeroldYale University, New Haven Connecticut, USA.
Wayne V MooreUniversity of Missouri, Kansas City, Kansas City, Missouri, USA.
Robin GolandColumbia University, New York, New York, USA.
Mark HarrisChildren's Health Queensland Hospital, South Brisbane, Australia.
Maria E CraigUniversity of Sydney, Sydney New South Wales, Australia.
Desmond A SchatzUniversity of Florida, Gainesville, Florida, USA.
David A BaidalUniversity of Miami, Coral Gables, Florida, USA.
Henry RodriguezUniversity of South Florida, Tampa, Florida, USA.
Kristina M UtzschneiderVA Puget Sound and the University of Washington, Seattle, Washington, USA.
Hendrik J NelUniversity of Queensland, Queensland, Brisbane, Australia.
Carol L SoppeImmune Tolerance Network, Seattle, Washington, USA.
Karen D BoyleRho, Inc, Durham, North Carolina, USA.
Karen CerosalettiCenter for Interventional Immunology and Diabetes Program, Benaroya Research Institute, Seattle, Washington, USA.
Lynette Keyes-ElsteinRho, Inc, Durham, North Carolina, USA.
S Alice LongCenter for Interventional Immunology and Diabetes Program, Benaroya Research Institute, Seattle, Washington, USA.
Ranjeny ThomasUniversity of Queensland, Queensland, Brisbane, Australia.
James G McNamaraNational Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Jane H BucknerCenter for Interventional Immunology and Diabetes Program, Benaroya Research Institute, Seattle, Washington, USA.
Srinath SandaImmune Tolerance Network, Seattle, Washington, USA.
ITN058AI EXTEND Study Team
Society of Interventional Radiology · USImmune Tolerance Network · USRho (United States) · USThe University of Queensland · AUUniversity of California, San Francisco · USChildren's Hospital of Philadelphia · USColumbia University · USJoslin Diabetes Center · USNational Institute of Allergy and Infectious Diseases · USRiley Hospital for Children · USSanford Health · USStanford University · USThe University of Sydney · AUThe University of Texas Southwestern Medical Center · USUniversity of Florida · USUniversity of Iowa · USUniversity of Miami · USUniversity of Minnesota · USUniversity of Missouri–Kansas City · USUniversity of Puget Sound · US

Funding

Immune Tolerance NetworkUM1AI109565 · NIAID · BENAROYA RESEARCH INST AT VIRGINIA MASON · 2022 to 2025
$94.0M
PILOT STUDY--SECRETORY TARGETING IN PANCREATIC B CELLSP30DK036836 · JOSLIN DIABETES CENTER · 1986 to 2025
$12.1M
Institutional Clinical and Translational Science AwardUL1TR001878 · UNIVERSITY OF PENNSYLVANIA · 2025 to 2025
$10.2M
Yale Clinical and Translational Science AwardUL1TR001863 · YALE UNIVERSITY · 2025 to 2025
$9.9M
NCATS NIH HHS UL1 TR000004NCATS NIH HHS UL1 TR000064NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR001863NCATS NIH HHS UL1 TR001878NCATS NIH HHS UL1 TR002494NCATS NIH HHS UL1 TR002529NCATS NIH HHS UL1 TR002537NCATS NIH HHS UL1 TR003142NIAID NIH HHS R01 AI132774NIAID NIH HHS UM1 AI109565NIAID NIH HHS UM2 AI117870NIDDK NIH HHS P30 DK036836NIDDK NIH HHS U01 DK085476NIDDK NIH HHS U01 DK103266
6 · The paper itself

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.

Indexed as

AdolescentB-Lymphocyte SubsetsChildDiabetes Mellitus, Type 1Double-Blind MethodFemaleHumansMaleReceptors, Interleukin-6Receptors, Interleukin-6Beta cellsDiabetesEndocrinologyImmunologyT cells

Identifiers

PMID34747368
PMCPMC8663550
OpenAlexW3212575051

What Socratic holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.