Diabetes and Metabolic Disorders: The Approval of Teplizumab

I.Diabetes and Metabolic Disorder Background

Diabetes is a chronic disorder that affects how the body handles blood glucose, which is the major source of energy for the body's cells, notably the brain and muscles (Lema-Pérez, 2021) (Mergenthaler, 2013). It manifests in two ways: inadequate insulin production by the pancreas or the body's inability to utilize insulin properly.  Insulin is a hormone that allows glucose to enter cells, where it is turned to energy.

There are two primary forms of diabetes:

● Type 1 diabetes is an autoimmune condition in which the immune system erroneously attacks and kills insulin-producing beta cells in the pancreas. As a result, people generate little or no insulin and must rely on insulin treatment throughout their lives to survive (Anderson, 2023). It usually appears in infancy or adolescence, however adult-onset instances may exist.

● Type 2 diabetes is distinguished by insulin resistance, a condition in which the body's cells do not respond appropriately to insulin. Initially, the pancreas adapts by making more insulin, but eventually, insulin production cannot keep up with the increased demand (Goyal, 2024). Type 2 diabetes is frequently associated with obesity, sedentary lifestyles, and eating choices.

Diabetes is classed as a metabolic condition since it causes abnormal glucose metabolism.  Other metabolic diseases include metabolic syndrome, which combines obesity, hypertension, dyslipidemia, and insulin resistance.  These metabolic abnormalities dramatically raise the risk of cardiovascular disease and associated consequences (Gao, 2025).

II.The Evolving Treatment Landscape for Type 1 Diabetes

Historically, insulin has been the foundation of Type 1 diabetes care.  Insulin treatment, which was discovered in the early 1920s, has saved many lives.  However, insulin therapy is neither a cure or disease-modifying treatment, but rather a management tool.  While insulin efficiently decreases blood glucose levels, it does not treat the underlying autoimmune etiology of Type 1 diabetes (Saleem, 2025).

Over the last several decades, innovations in glucose monitoring, insulin delivery devices, and supplementary drugs have improved patients' quality of life and glucose management.  Nonetheless, the evolution of autoimmune destruction of beta cells has gone neglected until recently.

III.The Breakthrough: Teplizumab

In November 2022, the United States Food and Drug Administration (FDA) approved Teplizumab (brand name: Tzield), the first disease-modifying medication for Type 1 diabetes (Evans-Molina, 2023). Teplizumab, developed by Provention Bio (later purchased by Sanofi), belongs to a novel class of immunomodulatory medicines that attempt to change the course of the illness rather than only manage symptoms (Sanofi, 2023).

Teplizumab is a monoclonal antibody that targets CD3, a protein located on the surface of T lymphocytes, which are responsible for the autoimmune destruction of pancreatic beta cells (Herold, 2019).  Teplizumab, by modifying T cell activity, can slow the course of Type 1 diabetes in people at high risk of acquiring the illness.

Mechanism of Action

Teplizumab works by binding to T cell CD3 receptors, partially deactivating them, and diverting the immune response away from aggressive, beta cell-destroying activity. This immune regulation prolongs the function of insulin-producing beta cells, delaying the need for insulin therapy in high-risk individuals (Chatenoud, 2012).

Teplizumab, by lowering the autoimmune attack on the pancreas, provides a window of protection during a critical stage in the development of Type 1 diabetes, potentially changing long-term results for people who take it (Pozzilli, 2012).

Clinical Trials and Efficacy

The critical Phase 2 trial, NCT01030861, tested Teplizumab in relatives of Type 1 diabetes patients who had at least two diabetes-related autoantibodies and dysglycemia, suggesting a very high chance of developing clinical diabetes (Herold, 2019). The study found that a single 14-day treatment of Teplizumab resulted in a median time to the diagnosis of type 1 diabetes of 4.03 years in the teplizumab group and 2.03 years in the placebo group; the disease was diagnosed in 19 (43%) of the participants who received teplizumab and in 23 (72%) of those who received placebo.

This was a historic breakthrough because no previous medication was found to modify the course of Type 1 diabetes development in at-risk patients. This experiment, known as TN-10, served as the basis for FDA clearance, and post-marketing studies are under underway to examine long-term effects and safety (Herold, 2019). That said, Provention Bio’s Biologics License Application (BLA) included integrated results from six clinical trials (TN-10, Delay, Encore, Protégé, AbATE, and a Phase I study), totaling 609 patients, which confirmed a median delay of 4.17 years versus 2.08 years for placebo and consistent beta cell preservation (Herold, 2023).

IV.The Approval and Its Implications

Teplizumab’s approval marks the first time a disease-modifying therapy has been introduced for Type 1 diabetes, ushering in a new era of preventative and immunotherapeutic strategies in this relatively rare form of diabetes. The implications extend beyond immediate treatment benefits:

● Preserving Beta Cell Function: By delaying illness onset, patients can extend endogenous insulin production, improving glycemic control and lowering the risk of complications (Sims, 2021).

● New avenues for early intervention: With increasing access to genetic and autoantibody screening, high-risk patients can now be identified early and provided a treatment alternative to slow disease development (Verge, 1996).

● Future Combinational therapy: Teplizumab opens the door to future research on combination therapy that might slow or even reverse Type 1 diabetes development (Christen, 2023).

 V. Limitations and Considerations

While Teplizumab represents a significant breakthrough, it is not without limitations:

● The present approval is limited to people aged 8 and above who have a high risk of acquiring Type 1 diabetes based on biomarker testing. It is not designed for people who already have Type 1 diabetes (Evans-Molina, 2023).

● Side Effects: As an immunomodulatory agent, Teplizumab can cause transient side effects such as rash, and leukopenia (low white blood cell count), however there is no evidence of increased risk of common infections such as SARS-CoV-2 (Sherry, 2011) (Ramos, 2023).

● Cost and Accessibility: Teplizumab was priced at $13,850 per vial, equivalent to almost $194,000 for a standard 14-day course (Taylor, 2022). For comparison the price per unit range of the 5 most popular drugs in the USA is $500–$6,000 (Rudy, 2025). That said biologics like Teplizumab can be expensive to manufacture, however, the popular and comparable biologic Humira is priced at only $3,500–$4,000 per unit (Anderson, 2024). Beyond T1Detect, TrialNet and ASK (Colorado), widespread screening for at-risk T1D individuals is not yet routine, posing challenges for implementation at the population level (Drivers, 2021).

VI. The Future of Type 1 Diabetes Care

Teplizumab's approval is a crucial milestone in diabetes care. It signifies a shift from reactive management of hyperglycemia to proactive intervention aimed at modifying disease progression. This paradigm shift has potential applications beyond Type 1 diabetes, as researchers continue to explore immunotherapies for other autoimmune and metabolic disorders such as rheumatoid arthritis (Notley, 2010).

Pharmaceutical companies are investing in next-generation immunotherapies, beta cell regeneration strategies, and combination approaches involving GLP-1 receptor agonists, SGLT-2 inhibitors, and other agents to preserve beta cell function and improve outcomes (Warshauer, 2020).

VII. Conclusion

The approval of Teplizumab as the first disease-modifying therapy for Type 1 diabetes marks a transformative moment in the treatment of autoimmune diabetes. By delaying the onset of clinical disease in high-risk individuals, Teplizumab offers hope for improved quality of life and reduced long-term complications.

As research advances and screening becomes more accessible, early immunotherapeutic intervention may soon become a standard strategy in managing Type 1 diabetes. While challenges remain in terms of cost, logistics, and long-term safety, Teplizumab has opened the door to a future where Type I diabetes prevention is within reach.

The dynamic landscape of diabetes and metabolic disorder treatments continues to evolve, driven by scientific innovation, pharmaceutical development, and an unwavering commitment to improving patient outcomes. Teplizumab represents not only a triumph of targeted immunotherapy but also a beacon for future breakthroughs in disease-modifying therapies.

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