Current perspectives and the future of disease-modifying therapies in type 1 diabetes

Abstract

Use of immunomodulating agents to prevent the progression of autoimmune β-cell damage leading to type 1 diabetes mellitus (T1DM) is an interesting area for research. These include non-specific anti-inflammatory agents, immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines. Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen. Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM. The benefits have been apparent as early as six months to as long as seven years after therapy. It has recently been approved by the Food and Drug Administration to delay the onset of clinical (stage 3) type 1 diabetes in children above 8 years of age. In their recent meta-analysis published in the World Journal of Diabetes, Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use, change in C-peptide response, and better glycemic control compared to the control group with a good safety profile. However, all the included randomized control trials have been conducted in high-income countries. High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.

Keywords: Teplizumab; Type 1 diabetes mellitus; Disease modifying therapy; β-cell function; C-peptide; Immunotherapy

Core Tip: Teplizumab is an anti-CD3 immunomodulator that can render the T cell anergic to its target antigen and thus protect against autoimmune beta cell destruction. It is approved for use in individuals aged above 8 years in early pre-clinical stages of type 1 diabetes mellitus to prevent progression to clinical stage (stage 3). C-peptide decline is halted and the need for insulin therapy can be delayed even after discontinuation of this therapeutic molecule. Adverse effects are mostly mild. The high cost and lack of availability limit its applicability in low- and middle-income countries.