Breakthroughs in the Management of Type 1 Diabetes

Innovations in Diabetes & Endocrinology | Winter 2023

Two first-in-class advancements in the management of Type 1 diabetes (T1D) are inspiring hope for delayed disease progression and improved glucose control.

In November, the Food and Drug Administration (FDA) approved Tzield™ (teplizumab-mzwv) as the first and only immunotherapy shown to delay progression to stage 3 T1D in appropriately selected patients. Administered as a daily injection over a single 14-day course, Tzield is a humanized CD3-directed monoclonal antibody indicated for patients aged 8 and older who have been diagnosed with stage 2 TID.

Yumiko Tsushima, MD

“Early Type 1 diabetes is diagnosed by the presence of antibodies before abnormal glucose control has manifested,” says Yumiko Tsushima, MD, a specialist in endocrinology within the University Hospitals Diabetes and Metabolic Care Center and Assistant Professor at Case Western Reserve University School of Medicine. “In the phase II trial studying teplizumab, patients with stage 2 Type 1 diabetes were randomized to receive teplizumab or placebo and were followed to their progression to stage 3, or Type 1 diabetes with overt hyperglycemia.” The trial recruited at-risk relatives of patients with T1D. Results¹ published in the New England Journal of Medicine (NEJM) demonstrated a statistically significant delay in progression to stage 3 TID.

Staging T1D

A chronic autoimmune disease, T1D causes the immune system to attack and destroy insulin-producing beta cells within the pancreas, leaving individuals with lifelong exogenous insulin dependency. Affecting more than 1.5 million Americans, T1D is defined by three stages:

Stage 1 – Patients test positive for two or more diabetes-linked autoantibodies but are asymptomatic and maintain normal glucose control.    

Stage 2 – Patients test positive for two or more diabetes-linked autoantibodies; glucose levels become abnormal as more beta cells are destroyed. Patients remain asymptomatic.

Stage 3 – Patients demonstrate overt hyperglycemia requiring insulin therapy, and a clinical diagnosis is established. Patients begin to experience symptoms that may include polyuria, polydipsia, weight loss, fatigue and diabetic ketoacidosis. The lifetime progression from stage 1 or 2 to stage 3 approaches 100 percent.

“The study of this novel immunotherapy in patients in the stage 2 phase showed the potential to delay onset of clinical diagnosis by up to two years,” says Dr. Tsushima. “That may not seem like a long time, but individuals with stage 3 diabetes require lifelong insulin therapy — through injections four or more times a day or an insulin pump — so any delay in the burden of diabetes management and complications is a tremendous advancement.”

An Investigational Bionic Pancreas

Developed by Beta Bionics, the iLet Bionic Pancreas is a closed-loop automated insulin delivery system granted Breakthrough Device status by the FDA in 2019. The device pairs a tubed insulin pump with a continuous glucose monitor and smartphone connectivity. “What differentiates the bionic pancreas from current semi-automated insulin delivery systems is that it simplifies user inputs,” says Dr. Tsushima. “Current systems require users to track and enter their daily carbohydrates, but the bionic pancreas delivers insulin autonomously based on body weight and patient-entered qualitative meal announcements. Over time, the device learns glucose patterns to further improve glycemic control.”

The NEJM recently published findings² from a multicenter, randomized trial that compared bionic pancreas treatment to standard care. Results of the 13-week investigation found that users of the iLet device experienced a greater reduction in glycated hemoglobin levels when compared to the control group. Participants using the bionic pancreas spent more time in the target range and less time in the hyperglycemia range without an increase in hypoglycemia.

Although the results of this study focused on insulin-only delivery, the device is configured with a dual pump and the capacity to deliver both insulin and glucagon. “Dual hormone systems are being studied, but larger and longer trials are still needed to determine whether this system is superior in managing glucose levels and reducing risk of hypoglycemic events,” says Dr. Tsushima. “These advancements represent the next generation of Type 1 diabetes care and have the potential to offer children and adults living with the condition the opportunity for improved glucose management and quality of life.”

For more information, contact Dr. Tsushima at Yumiko.Tsushima@UHhospitals.org.

¹ An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med 2019; 381:603-613. DOI: 10.1056/NEJMoa1902226

² Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes. N Engl J Med 2022; 387:1161-1172. DOI: 10.1056/NEJMoa2205225

Contributing Expert:
Yumiko Tsushima, MD
University Hospitals Diabetes and Metabolic Care Center
University Hospitals Cleveland Medical Center
Assistant Professor, Case Western Reserve University School of Medicine