Drug therapies in pre-clinical stages of type 1 diabetes

Abstract

Type 1 diabetes is a multifactorial heterogenous autoimmune disease characterized by progressive pancreatic beta-cell loss and a requirement of lifelong insulin therapy. A paradigm shift is occurring in how we treat type 1 diabetes, in addition to replacing insulin at the clinical onset (Stage 3), addressing the underlying autoimmune process earlier in the disease (Stage 1 or 2).

Teplizumab, a humanized monoclonal anti-CD3 antibody, is the first approved disease-modifying treatment of preclinical stage 2 diabetes, now available in several countries. In a phase 2 randomized control trial, a 14-day course delayed the median time to clinical diabetes by more than two years and was associated with a reduced risk of progression compared to placebo. Research of drugs like antithymocyte globulin (ATG), (an antibody preparation used in solid organ transplantation), golimumab, (a monoclonal antibody specific for TNF alpha, a proinflammatory cytokine), baricitinib, (a tyrosine kinase inhibitor), among others is ongoing.

Multicenter, multinational studies such as TrialNet and INNODIA have been instrumental in advancing this field. The focus of new strategies will certainly increasingly be on personalized combination therapy of immune modulatory drug. Early intervention holds promise for delaying or preventing immune-mediated disease onset and improving clinical outcomes. Yet gaps remain, including limited long-term follow-up., and need to refine risk stratification. With continued progress and efforts, early intervention could shift the paradigm from disease management to delay/prevention in type 1 diabetes.