Low-Dose IL-2 and Beta-Cell Function in Newly Diagnosed T1D
Michelle Rosenzwajg, Agnès Hartemann, Marine Halbron, Chloé Amouyal, Charles Thivolet, Vincent Rigalleau, Pierre Fontaine, Brigitte Mignot, Rachel Reynaud, Jean-Claude Carel, Elise Bismuth, Caroline Storey, Karine Bourdet, Emmanuel Sonnet, Sabine Baron, Marc Nicolino, Kevin Perge, Lucy Chaillous, Laurence Kessler, Marie Mansilla, Peter Achenbach, Anette-Gabriele Ziegler, Henk-Jan Aanstoot, Thierry Mouraux, Kristina Casteels, Marc Y Donath, Bart O Roep, Roberta Lorenzon, Claire Ribet, Joe-Elie Salem, Fabien Pitoiset, Alexandra Roux, Eric Vicaut and David Klatzmann, on behalf of the DIABIL-2 investigators
Efficacy and safety of low-dose IL-2 in people with newly diagnosed type 1 diabetes (DIABIL-2): a double-blind, multicentre, randomised, placebo-controlled, phase 2b trial. The Lancet Diabetes & Endocrinology. Published online October 1, 2026. Online ahead of print.
Type 1 diabetes (T1D) is caused by an autoimmune response that progressively destroys insulin-producing beta cells. Regulatory T cells (Tregs) normally help control unwanted immune responses, but their function can be impaired in T1D. Low doses of interleukin-2 (IL-2) can selectively stimulate these Tregs and have therefore been proposed as a potential way to slow the autoimmune process and preserve the body’s remaining insulin production. Rosenzweig - Efficacy and safet…
The DIABIL-2 trial investigated whether low-dose IL-2 could preserve beta-cell function in people recently diagnosed with T1D. This phase 2b trial included 141 participants aged 6–35 years from 19 centres in five European countries. Participants received low-dose IL-2 either weekly or every two weeks for approximately one year, or placebo. The main outcome was preservation of C-peptide, a marker of the body’s own insulin production. Diabeter’s Henk-Jan Aanstoot was one of the investigators participating in the multicentre study.
Key findings:
- Low-dose IL-2 successfully stimulated regulatory T cells: Treatment produced a marked increase in Tregs shortly after initiation and sustained an approximately 20% increase in Treg frequency, confirming that IL-2 had the intended biological effect.
- However, this did not translate into preservation of beta-cell function: After 12 months, there was no statistically significant difference in stimulated C-peptide between participants receiving IL-2 and placebo. Similar results were found for the two dosing regimens and across age groups.
- Other metabolic outcomes showed no clear benefit: HbA1c, insulin dose-adjusted HbA1c and fasting glucose did not show consistent improvements with IL-2. There was also no significant relationship between the increase in Tregs and changes in C-peptide, HbA1c or daily insulin requirements.
- Low-dose IL-2 was well tolerated: The treatment showed a favourable safety profile in both children and adults. Injection-site reactions were common, but no participants needed dose reductions or stopped treatment because of drug-related toxicity.
- Timing and treatment strategy may be crucial: The researchers suggest that the inflammatory autoimmune response around the time of T1D diagnosis may be too strong for stimulation of Tregs alone. Low-dose IL-2 might therefore be more effective earlier in the disease process, before clinical diagnosis, or as part of a combination or sequential immunotherapy strategy.
The DIABIL-2 study shows an important distinction between biological activity and clinical benefit: low-dose IL-2 clearly affected the immune system as intended, but this alone was not enough to preserve insulin production after T1D diagnosis. Its favourable safety profile nevertheless supports further research into earlier intervention and combination therapies.
Concluding, the authors state
“The confirmed target engagement, excellent safety profile, and efficacy of low-dose IL-2 in other autoimmune and inflammatory conditions support continued investigation of this approach using alternative regimens, combination strategies, earlier intervention, and prevention in presymptomatic populations.”
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