Evidence mapPaperPMID 41563349Full record

Trial reportDiabetes care2026

Effect of High-Dose Oral Insulin in Children With Stage 1 Type 1 Diabetes: The Fr1da Insulin Intervention Randomized Controlled Trial.

Anette-Gabriele Ziegler, Ali Albeer, Stefanie Arnolds, Robin Assfalg, Melanie Bunk, Carolin Daniel, Anna Hofelich, Stefanie Jacobsen, Kerstin Kick, Jan Knoop and 14 more

Abstract readRandomized Controlled TrialClinical Trial, Phase II
In one paragraph

Trial report in Diabetes care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Anette-Gabriele ZieglerInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.ORCID 0000-0002-6290-5548
Ali AlbeerInstitute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig Maximilian University, Munich, Germany.
Stefanie ArnoldsInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Robin AssfalgInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Melanie BunkInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Carolin DanielGerman Center for Diabetes Research, Neuherberg, Germany.
Anna HofelichForschergruppe Diabetes, School of Medicine and Health, Technical University of Munich (TUM) and TUM University Hospital, Munich, Germany.
Stefanie JacobsenInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Kerstin KickInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Jan KnoopInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Mirjam KohlsInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Olga KordonouriKinder- und Jugendkrankenhaus Auf der Bult, Hanover, Germany.ORCID 0000-0001-9563-3537
Claudia MatzkeInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Markus PfirrmannInstitute for Medical Information Processing, Biometry, and Epidemiology, Faculty of Medicine, Ludwig Maximilian University, Munich, Germany.
Claudia RammingerInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Katharina SarclettiInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Marlon ScholzInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Katharina Schütte-BorkovecInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Isabelle SerrGerman Center for Diabetes Research, Neuherberg, Germany.
Marc WeigeltCenter for Regenerative Therapies Dresden, Dresden University of Technology, Dresden, Germany.
Andreas WeissInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Christiane WinklerInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.
Ezio BonifacioGerman Center for Diabetes Research, Neuherberg, Germany.ORCID 0000-0002-8704-4713
Peter AchenbachInstitute of Diabetes Research, Helmholtz Munich, German Research Center for Environmental Health, Neuherberg, Germany.ORCID 0000-0001-6720-2684

Funding

Breakthrough T1D JDRF 3-SRA-201572-M-RLeona M. and Harry B. Helmsley Charitable Trust G-19113274Leona M. and Harry B. Helmsley Charitable Trust G-2016PG-T1D020Leona M. and Harry B. Helmsley Charitable Trust G-2017PG-T1D023
6 · The paper itself

Abstract

objectiveOral administration of an antigen can induce immunological tolerance. Insulin is an autoantigen in childhood type 1 diabetes (T1D). We tested the effect of treatment with high-dose oral insulin on disease progression and immune response to insulin in children with stage 1 T1D. RESEARCH DESIGN AND

methodsWe conducted a phase 2 randomized placebo-controlled double-blind trial in children with stage 1 T1D who received daily oral insulin (7.5 mg/day for 3 months and 67.5 mg/day for 9 months; n = 110) or placebo (n = 110) for 12 months. The coprimary outcomes were 1) time from baseline to dysglycemia or clinical diabetes and 2) increased immune response to insulin within 12 months of treatment (assessed in the first 90 participants).

resultsOf 220 participants (112 girls; median age 4.8 years; interquartile range 3.6, 6.2), 179 completed the trial. Dysglycemia or diabetes developed in 87 participants (46 receiving oral insulin and 41 receiving placebo; hazard ratio 1.07; 95% CI 0.66-1.73; P = 0.74). The 5-year progression rate was 40% (95% CI 30-51%) in each group. A modest treatment interaction was found with the INS rs689 genotype (P = 0.03). Increased immune response to insulin was observed in 11 (25%) of 44 participants in the oral insulin group and 13 (31%) of 42 in the placebo group (P = 0.63). Oral insulin was well tolerated. No significant study-related adverse events occurred.

conclusionsIn children with stage 1 T1D, 1 year of high-dose oral insulin did not alter progression to dysglycemia or diabetes or immune response to insulin.

Indexed as

Diabetes Mellitus, Type 1Hypoglycemic AgentsInsulinAdministration, OralChildChild, PreschoolDouble-Blind MethodFemaleHumansMaleHypoglycemic AgentsInsulin

Identifiers

PMID41563349
PMCPMC13094874

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.