Significance of Bacillus Calmette-Guerin (BCG) vaccine intervention for patients with Type 1 Diabetes (T1D): A systematic review and meta-analysis

Purpose: Immunotherapy is an emerging therapeutic modality for many autoimmune, oncology, and infectious diseases to cure or prevent the underlying causes. Several immunotherapeutic agents are investigated for their beneficial potential in patients with diabetes. However, none have culminated into a successful therapy. The present comprehensive meta-analysis and systematic review covers the last two decades of historical research evaluating the Bacillus Calmette-Guerin (BCG) vaccine as an immunotherapeutic agent in diabetes, along with updated information on similar recent publications. Method: A total of 278 articles were retrieved through literature databases, and after applying inclusion and exclusion criteria as per PRISMA guidelines, seven studies were selected for meta-analysis using Cochrane Q statistics. Results: Our meta-analysis revealed marginal benefits, lowering glycosylated/glycated haemoglobin (HbA1C) levels and glutamic-acid-decarboxylase (GAD) auto- antibodies in BCG treated people with Type 1 Diabetes (T1D) compared to the matched control individuals. The BCG intervention found to be ineffective in regulating C-peptide (connecting peptide) and clinical remission (CR) i.e. improved glycemic regulation, though beneficial tendency was observed. Conclusion: Our systematic review and meta-analysis revealed benefits of BCG vaccine intervention in T1D patients, including improved HbA1C and GAD autoantibody levels. However, the study has several limitations stemming from BCG vaccine-related factors and patient characteristics. Therefore, a large clinical trial with an enhanced study design is needed to validate the immunity-related benefits of the BCG vaccine for glucose metabolism in patients with T1D.