Systematic review finds BCG vaccination's immunometabolic benefits in type 1 diabetes contradicted by observational data

The global incidence of Type 1 Diabetes (T1D) continues to rise, driven by autoimmune destruction of pancreatic β-cells. Current treatments primarily focus on insulin replacement, but there remains a critical need for adjunctive therapies that can halt or reverse the autoimmune process and preserve β-cell function. Bacille Calmette-Guérin (BCG) vaccination, traditionally used for tuberculosis, has shown immunomodulatory properties, including the induction of TNF and Treg cells, which could potentially mitigate the autoimmune attack in T1D and improve metabolic control.

This systematic review critically evaluated the role of Bacille Calmette-Guérin (BCG) vaccination in the prevention and adjunctive treatment of Type 1 Diabetes (T1D). Researchers performed a comprehensive literature search across PubMed, Google Scholar, and Cochrane databases. The inclusion criteria encompassed clinical trials, cohort, case-control, and epidemiological studies published in English between 1969 and May 2026, focusing on immunomodulatory and metabolic mechanisms of BCG in T1D.

The evidence regarding BCG vaccination in Type 1 Diabetes (T1D) was highly heterogeneous and divided into supportive and opposing findings. Supportive studies, primarily interventional and mechanistic, reported significant improvements in C-peptide levels, reductions in HbA1c, and partial β-cell recovery. These studies also highlighted immune modulation via TNF induction, Treg activation, and increased glycolysis as key mechanisms.

In contrast, opposing evidence, largely derived from large observational cohorts and some randomized trials, showed no significant association between BCG vaccination and reduced incidence or progression of diabetes. Overall, the findings exhibited considerable inconsistencies across study designs, patient populations, and follow-up durations, leading to conflicting conclusions regarding BCG's efficacy in T1D.