Evidence map›Paper›PMID 40598585›Full record

SynthesisBMC medicine2025

A systematic review and network meta-analysis of interventions to preserve insulin-secreting beta cell function in people newly diagnosed with type 1 diabetes: results from randomised controlled trials of immunomodulatory therapies.

Sophie E Beese, Malcolm J Price, Claire Tomlinson, Pawana Sharma, Isobel M Harris, Ada Adriano, Lauren M Quinn, Ritu Gada, Thomas J Horgan, Fiona Maggs and 6 more

Abstract readSystematic ReviewNetwork Meta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in BMC medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 2 pooled it
–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

6 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Review
  4. Article
  5. Observational
  6. 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

16 authors.

Sophie E BeeseDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK. s.beese@bham.ac.uk.
Malcolm J PriceDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Claire TomlinsonDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Pawana SharmaDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Isobel M HarrisDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Ada AdrianoDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Lauren M QuinnDepartment of Immunology and Immunotherapy, University of Birmingham, and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Ritu GadaDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Thomas J HorganDepartment of Oral and Maxillofacial Surgery, Shrewsbury and Telford Hospital NHS Trust, Telford, UK.
Fiona MaggsDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Martin BurrowsDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Krishnarajah NirantharakumarDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
G Neil ThomasDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK.
Robert C AndrewsUniversity of Exeter Medical School, Exeter, UK.
David J MooreDepartment of Applied Health Sciences, School of Health Sciences, University of Birmingham, Birmingham, B15 2TT, UK. d.j.moore@bham.ac.uk.
Parth NarendranDepartment of Immunology and Immunotherapy, University of Birmingham, and University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.

Funding

Breakthrough T1D 201311771National Institute for Health and Care Research PB-PG-0317-20046
6 · The paper itself

Abstract

backgroundType 1 diabetes is characterised by the immune-mediated destruction of pancreatic beta cells. We aimed to determine the effectiveness of immunotherapies for preserving residual beta cell function in newly diagnosed (stage 3) type 1 diabetes.

methodsSearches were carried out in MEDLINE, Embase, Cochrane CENTRAL and trial registries until 31st Jul 2024. RCTs of immunotherapies to preserve beta cells in newly diagnosed type 1 diabetes were included. Data were extracted using a bespoke, piloted extraction sheet. Risk of bias was assessed using Cochrane Risk of Bias Tool 1. A random effects network meta-analysis was undertaken in R. The primary outcome was C-peptide. Interventions were analysed by class.

resultsSixty trials were included (4597 patients, 32 intervention classes). Forty-one trials of 42 interventions were eligible for network meta-analysis. Eleven interventions demonstrated statistically significantly higher levels of C-peptide than placebo at 12 months, mesenchymal stem cells (autologous and Wharton's jelly-derived cells), azathioprine, interferon-alpha (5000 IU), autologous dendritic cells, anti-TNF golimumab, low-dose ATG, 3 mg 1-course anti-CD3 teplizumab, baricitinib, cyclosporin and 9/11 mg 2-course anti-CD3 teplizumab but with substantial heterogeneity present (I

conclusionsEleven of 42 interventions demonstrated statistically significantly higher C-peptide levels than placebo at 12 months in the network meta-analysis. These results have identified the 11 most promising therapies trialled and help to direct future head-to-head clinical trials to support approvals for interventions to treat those newly diagnosed with type 1 diabetes. However, data for some interventions originated from small studies (mesenchymal stem cell therapies, azathioprine, autologous dendritic cells) and findings should be considered as hypothesis generating and interpreted with caution due to evidence heterogeneity. SYSTEMATIC REVIEW REGISTRATION: The protocol for the systematic review was registered on PROSPERO, the international database of prospectively registered systematic reviews (registration: CRD42018107904).

Indexed as

Diabetes Mellitus, Type 1ImmunotherapyInsulin-Secreting CellsC-PeptideHumansRandomized Controlled Trials as TopicC-PeptideBeta cellsNetwork meta-analysisSystematic reviewType 1 diabetes

Identifiers

PMID40598585
PMCPMC12211534

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.