Efficacy and Safety of Regulatory T-cell Therapies in Type 1 Diabetes: A Systematic Review and Meta-analysis
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Background: Type 1 diabetes mellitus results from autoimmune destruction of pancreatic beta cells, leading to lifelong insulin dependence. Regulatory T cells (Tregs) play a central role in maintaining immune tolerance and are promising therapeutic targets for the preservation of endogenous insulin production. Objective: To evaluate the efficacy and safety of regulatory T-cell-based therapies in patients with type 1 diabetes through a systematic review and meta-analysis. Methods: We conducted a systematic search of the PubMed, Embase, and Cochrane CENTRAL databases until January 23, 2025.We included randomized controlled trials and prospective studies investigating Treg therapies (adoptive transfer, low-dose IL-2, anti-CD3, and combination approaches) in patients with type 1 diabetes. The primary outcome was C-peptide preservation at 12 months. We performed a random-effects meta-analysis and assessed the quality of evidence using the GRADE methodology. Results: Nine studies with 126 participants met the inclusion criteria. A meta-analysis of C-peptide preservation (three studies, 70 participants) demonstrated a large beneficial effect favoring Treg therapy, a with standardized mean difference of 1.07 (95% CI: 0.55-1.58, P < 0.0001). No heterogeneity was observed between the studies (I² = 0%). Serious adverse events occurred in four of the 126 participants (3.2%), primarily hypoglycemic episodes. IL-2 therapy achieved dose-dependent Treg expansion, ranging from 45% to 77% in the present study. The GRADE assessment indicated moderate-certainty evidence for C-peptide preservation and safety. Conclusions: Regulatory T-cell therapies substantially preserve pancreatic beta-cell function and have an acceptable safety profile. The large effect size and excellent consistency across intervention types support the progression to larger phase III trials to establish optimal treatment protocols and confirm these promising results.
