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Article History

Received: 1 December 2025

Accepted: 20 March 2026

First Online: 18 May 2026

Acknowledgements

: The authors would like to acknowledge the Medical University of Lodz – Digital Medicine Center (MULDiMediC) project (2023/ABM/02/00009) financed by the Medical Research Agency in Poland for access to its computational resources. We thank A. Demarré and V. Laurysens (BENE, Vrije Universiteit Brussel, Brussels, Belgium) and J. Laureys (Leuven Diabetes Lab, KU Leuven, Leuven, Belgium) for their valuable technical help. We thank N. Vandermeulen and K. Vandereyken (KU Leuven Institute for Single Cell Omics [LISCO], KU Leuven, Leuven, Belgium) for support on the Visium technique. The graphical abstract and Fig. a were created with BioRender.com.

: The Visium data and code generated in this study are deposited at the RDR repository of KU Leuven and are available via 10.48804/CBE1UC. Other data that support the findings of this study are available upon request. All data are archived in the VUB/KUL Institution Data Repository in a FAIR-compliant manner and are available from the corresponding authors upon request. There are no restrictions on data availability.

: The codebase is available at .

: This work was funded by Breakthrough T1D (2-SRA-2022-1200-S-B: ‘SyneRegIm: exploring the SYNErgistic effect of beta cell REGeneration and emerging IMmune intervention strategies to prevent and/or reverse type 1 diabetes’). This work was supported by research and infrastructure grants from KU Leuven (C1/18/006 and C16/24/012, and KA/20/077). This work was supported by grants from the Research Foundation Flanders (FWO) (1806426N and G058122N) and Breakthrough T1D (5-CDA-2024-1491-S-B) to WS. NDL is supported by FWO through grant G099323N. JC is supported by the Foundation for Polish Science START programme, a National Science Centre PRELUDIUM BIS 4 (2022/47/O/NZ5/00683) grant, a Polish Ministry of Science and Education ‘Perły Nauki 1’ (PN/01/0025/2022) grant, an ISPAD-Breakthrough T1D fellowship, CRIDO ‘Korzenie Przyszłości’ and a Medical University of Lodz BRaIn P1 grant. SB, AVM, SC and LW are doctoral fellows from FWO with grant numbers 1S89821N, 11I3123N, 11P3Z24N and 11J7425N, respectively.

: CM serves or has served on the advisory panel for Novo Nordisk, Sanofi, Eli Lilly and Company, Novartis, Dexcom, Boehringer Ingelheim, Bayer, Roche, Abbott, Medtronic, Insulet Biomea Fusion, SAB Bio, vTv Therapeutics and Vertex. Financial compensation for these activities has been received by KU Leuven. KU Leuven has received research support for CM from Dexcom, Novo Nordisk and Sanofi. CM serves or has served on the speakers bureau for Novo Nordisk, Sanofi, Eli Lilly and Company, Medtronic, Dexcom, Insulet, Abbott, Vertex and Boehringer Ingelheim. Financial compensation for these activities has been received by KU Leuven. CM is president of EUDF. All external support of EUDF is to be found on . WS serves on the advisory board for Sanofi. Financial compensation for these activities has been received by UZ Brussel. The authors declare that there are no other relationships or activities that might bias, or be perceived to bias, their work.

: All authors have contributed substantially to this study. CM, WS, CG and NDL were responsible for the conceptualisation and design of the project. LD, AW, SB and MV performed the in vivo data curation, while JC and PL conducted the spatial transcriptomics analyses. Figure creation for spatial transcriptomics was done by JC. Immunostaining was carried out by LD, JP, SC, LW and MP. Fiji scripts were designed by LD, AVM and GL, and the immunostaining analyses were performed by LD. Insulitis scorings were conducted by LD and MP. Data were visualised by LD and interpreted by LD, YH, CM, WS, CG and NDL. JDD and BY synthesised, characterised and provided the GLP1-E2 compound and gave scientific input on its use. LD oversaw project administration and prepared the original manuscript draft, and all authors contributed to reviewing and editing the final text. Funding was acquired by CM, WS, CG and NDL. CG and NDL are the guarantors of this work. All authors approved the final version of this manuscript.