Anti-CD3 monoclonal antibodies for the prevention and treatment of type 1 diabetes: A literature review

Am J Health Syst Pharm. 2022 Nov 22;79(23):2099-2117. doi: 10.1093/ajhp/zxac244.


Purpose: Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of beta cells, resulting in a loss of insulin production. Patients with T1D carry a substantial disease burden as well as substantial short-term and long-term risks associated with inadequate glycemic control. Currently, treatment mainly consists of insulin, which only treats the symptoms of T1D and not the root cause. Thus, disease-modifying agents such as anti-CD3 monoclonal antibodies (mAbs) that target the autoimmune destruction of beta cells in T1D would provide significant relief and health benefits for patients with T1D. This review summarizes the clinical evidence regarding the safety and efficacy of anti-CD3 mAbs in the prevention and treatment of T1D.

Summary: A total of 27 studies reporting or evaluating data from clinical trials involving otelixizumab and teplizumab were included in the review. Anti-CD3 mAbs have shown significant benefits in both patients at high risk for T1D and those with recent-onset T1D. In high-risk populations, anti-CD3 mAbs delayed time to diagnosis, preserved C-peptide levels, and improved metabolic parameters. In recent-onset T1D, anti-CD3 mAbs preserved C-peptide levels and reduced insulin needs for extended periods. Anti-CD3 mAb therapy appears to be safe, with primarily transient and self-limiting adverse effects and no negative long-term effects.

Conclusion: Anti-CD3 mAbs are promising disease-modifying treatments for T1D. Their role in T1D may introduce short-term and long-term benefits with the potential to mitigate the significant disease burden; however, more evidence is required for an accurate assessment.

Keywords: anti-CD3; monoclonal antibodies; otelixizumab; teplizumab; type 1 diabetes.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • C-Peptide / metabolism
  • C-Peptide / therapeutic use
  • CD3 Complex / therapeutic use
  • Diabetes Mellitus, Type 1* / diagnosis
  • Diabetes Mellitus, Type 1* / drug therapy
  • Diabetes Mellitus, Type 1* / prevention & control
  • Humans
  • Insulin / therapeutic use


  • C-Peptide
  • CD3 Complex
  • Antibodies, Monoclonal
  • Insulin