Yale researcher details clinical trial results for those just diagnosed with the condition.
[Originally published: Dec. 7, 2022. Updated: Oct. 20, 2023]
In 2022, the Food and Drug Administration (FDA) approved a medication that can delay the onset of type 1 diabetes—marking the first treatment to change the course of this autoimmune disease since the discovery of insulin in 1922.
The medication, called teplizumab and sold under the brand name Tzield®, is for people (ages 8 and up) with stage 2 type 1 diabetes, and researchers have been continuing to study how it can further help children and adolescents newly diagnosed with the disease.
To that end, a study published in mid-October in the New England Journal of Medicine (NEJM) was promising, finding that two 12-day courses of teplizumab in children and adolescents diagnosed with diabetes less than six weeks earlier preserved their ability to make their own insulin.
In type 1 diabetes, the beta cells in the pancreas make little to no insulin, a hormone needed to help glucose (blood sugar) enter the body’s cells so that it can be used for energy. Without insulin, blood sugar builds up in the bloodstream, leading to a variety of symptoms.
There are different stages of type 1 diabetes. In stage 1, blood sugar levels are normal, but autoantibodies—markers of disease activity—to insulin-producing beta cells have started to appear in the bloodstream, setting the stage for the killing of beta cells and a progression to stages 2 and 3, explains Kevan Herold, MD, a Yale Medicine endocrinologist who was involved in the teplizumab trials and was an author of the latest NEJM study (called PROTECT).
“During stage 2, the attack on the beta cells has progressed, but blood sugars are still normal—unless a certain kind of test, such as a glucose tolerance test, identifies impairment in beta cell responses,” says Dr. Herold. "The risk of developing stage 3, or clinical diabetes, within two years is about 50%."
The goal of teplizumab is to delay the onset of clinical diabetes, with the classic symptoms of excessive urination and thirst and other complications, as long as possible. Researchers say the drug postpones the median onset of the disease by at least two years.
Most who will develop type 1 diabetes do not have a relative with the disease and might not know they are at risk for its diagnosis. “Therefore, most patients arrive at a physician’s office or emergency room with stage 3 type 1 diabetes in which the classic symptoms of the disease, including diabetic ketoacidosis—a serious diabetes-related complication—have already appeared,” adds Dr. Herold.
In the PROTECT trial, teplizumab was given to children and adolescents with stage 3 type 1 diabetes to test whether the medication would stem the killing of beta cell function even after the diagnosis.
“This drug helps preserve someone’s ability to make their own insulin. We know that, particularly with kids with new-onset diabetes, they lose that ability over a period of years,” Dr. Herold says. “This doesn’t stop it completely, but it slows down the process, buying time in which their own pancreas is functioning. This is very helpful to children and adults with new-onset diabetes since a person’s pancreas is always better at delivering insulin than using artificial means.”
How does this new diabetes medication work?
Teplizumab is a monoclonal antibody that modifies T cells to prolong the pancreas’ ability to create insulin. The drug is specific to a molecule called CD3, which is the “cognate” component of the T cell, Dr. Herold explains. This modulates the immune cells and prevents them from attacking the cells in the pancreas that produce insulin.
The medication is delivered through a daily infusion for 12 days and does not need to be taken continuously, which is another benefit as many treatments need to be done every day, Dr. Herold says.
Why is this type 1 diabetes development important?
“Diabetes is a disease that is with you literally every minute of the day. You don’t sleep, exercise, or eat without thinking about your metabolic control,” says Dr. Herold. “People with diabetes will tell you that any time without the disease is a gift, particularly for young children and their parents. Some ask, ‘If you’re still going to get diabetes, what’s the big deal?’ But when you’re an eight-year-old child, if the time at which you need to take insulin, follow a prescribed diet, and monitor your blood sugar is delayed for two more years, that’s huge. Half of our patients have experienced a delay of even greater periods of time—even as long as 11 years.”
In childhood, those extra years matter—a high-schooler, for instance, may be better equipped to handle the burden of a chronic disease than a middle-schooler. The delay also reduces the time a patient is exposed to the high blood sugars that cause a wide range of health complications. As therapies for diabetes continue to evolve, there will likely be more improved and convenient options for patients.
How does teplizumab help those recently diagnosed with type 1 diabetes?
The PROTECT trial included 328 patients ages 8 to 17 who were randomly assigned to receive teplizumab or a placebo for two 12-day courses 26 weeks apart. (The pandemic lengthened the time to 52 weeks for some patients.)
The trial showed that the course of medication was successful in preserving beta cell function. Participants who received teplizumab also were able to reduce their use of insulin, had a lowered risk of severe hypoglycemia (low blood sugar), and were more likely to spend more time in their target glucose range. Furthermore, those who received the drug were more likely to reach the clinical threshold for disease remission, and they showed improvement in quality-of-life measures.
What’s next for type 1 diabetes treatment?
Dr. Herold says the promising news with teplizumab is that it is the starting point to prevent the disease from occurring or even to restore lost beta cells. Combining treatments may prolong and enhance responses in those at risk for type 1 diabetes. In addition, replacing the insulin-producing cells that have been destroyed—even with stem cell-derived beta cells, together with teplizumab, may be an effective combination, he adds.
“This is an exciting step toward our goal of eliminating type 1 diabetes,” says Dr. Herold, who is also a member of Yale’s Human and Translational Immunology Program, which works to accelerate the application of developments in the field of immunology to treat diseases.