A breakthrough in Type 1 diabetes: What it might mean for children
November 6, 2019
Nearly 100 years after the discovery of insulin therapy, an exciting new immunotherapy is providing hope of delaying – or even preventing – the onset of Type 1 diabetes in children.
Teplizumab, an immunotherapy drug, has shown in a clinical trial that it can slow the development of Type 1 diabetes (T1D) by two years.
A landmark study published in the August 2019 issue of the New England Journal of Medicine (NEJM) investigated the preventive effects of teplizumab on participants who’d had a relative diagnosed with T1D. Relatives of individuals diagnosed with T1D are 15 times greater risk than the general population to develop the disease, according to the American Diabetes Association.
Researchers found that teplizumab reduced the risk of being diagnosed by T1D during the study by 59% compared with subjects who received placebo. Participants randomized to teplizumab developed T1D an average of 48.4 months after receiving treatment, while those on placebo were diagnosed 24.4 months after starting the study. The drug essentially gave the teplizumab-treated subjects two more years on average to live free from diabetes.
Previous studies published in Lancet and Diabetes found that teplizumab can prolong insulin production in subjects recently diagnosed with T1D. However, the NEJM trial is the first to assess the effects of teplizumab in healthy, high-risk relatives.
More than 70% of the 76 enrolled participants were younger than 18, which is exciting because T1D is among the most common chronic conditions that develop in childhood, affecting approximately 200,000 children in the U.S. This landmark study is a major step forward in diabetes research and opens exciting possibilities for prevention and future health.
How teplizumab works, plus benefits and questions
Individuals who develop T1D generally have antibodies (biomarkers) that are associated with the disease. Patients with two antibodies have a 44% risk of developing T1D within five years; 70% risk in 10 years, and a 100% risk within their lifetime.
Teplizumab changes an individual’s autoimmune response – by altering the T lymphocytes that target the insulin-producing cells of the pancreas in T1D, the body is able to maintain insulin production longer.
Immediate benefits
The average age of T1D diagnosis is 13 – a tough age for children and families in general, and particularly for managing the complexities of diabetes. Hormone changes and growth spurts can require frequent blood sugar monitoring and insulin dosage adjustments. Sometimes families will need to work with coaches and teachers to accommodate nutritional and testing needs at school.
Delaying the onset of Type 1 diabetes can give teens more time to mature and learn about the condition.
Long-term benefits
The earlier in life that a person develops diabetes-related antibodies, the greater the risk of developing T1D. For example, an individual with two antibodies at 9 months old has a 50% risk of developing T1D within two years. Developing two antibodies at 5 years old, however, carries less than 10% risk of developing the disease within two years.
Similarly, the earlier in life that the disease develops, the greater the risk of developing complications related to T1D. Individuals with diabetes are at increased risk for:
- Diabetic eye disease such as diabetic retinopathy can result in vision damage and vision loss.
- Diabetic kidney disease affects approximately 1 in 4 adults with diabetes and causes complications with blood pressure and urination issues and can lead to kidney failure.
- Nerve damage (neuropathy) is a result of chronic high blood sugar and can result in pain, numbness, and a loss of sensation in the limbs and feet.
- Pancreatic complications, such as chronic pancreatitis, that progressively damage the organ and cause abdominal pain and diarrhea.
- Wounds on the feet caused by blisters or stepping on objects can develop into ulcers if left untreated. Patients might not notice wounds right away because of neuropathy. The American Podiatric Medicine Association states that foot ulcers lead to 85% of diabetes-related amputations.
Two key questions
If this therapy is approved by the U.S. Food and Drug Administration (FDA) in the future, patients and doctors will need to consider two key questions.
1. Do the risks outweigh the benefits?
Though there are many potential benefits of T1D delay or prevention with teplizumab, there are risks associated with immunotherapy drugs. Recipients might experience adverse and unpredictable reactions, such as headache, nausea, upper respiratory tract infection, low white blood cell count, and severe rashes. Most subjects in the trial who experienced side effects had mild symptoms that resolved within a few weeks. The most common adverse reactions in the patients treated with teplizumab were transient low lymphocyte counts and rash, but there was no increase in infections compared with placebo.
2. Should everyone at risk for T1D be treated?
Thinking down the road, it will become important to raise awareness about testing for the antibodies that indicate risk. We can identify at-risk individuals if a relative has been diagnosed with T1D. At UT Southwestern, we offer to check first-degree relatives of all our T1D patients for T1D-related antibodies.
However, if individuals don’t know their family history regarding diabetes, it will be difficult to identify at-risk individuals and determine which of these people will benefit most from treatment.
In individuals at high risk for developing T1D, the benefit of potentially delayed onset of T1D would have to be weighed against the possible risks of teplizumab therapy. If the drug is approved, patients and families should discuss this balance with their endocrine provider.
The future of teplizumab and T1D
Participants in the Phase II study completed just one 14-day cycle of treatment with impressive results. The next step will be a Phase III trial with a larger base of participants. The PROTECT Phase III trial, which will take place at 32 locations across the country, has a goal of enrolling 300 participants and is projected to be complete some time in 2022. If the results are positive, the drug can be submitted for approval to FDA. Find a trial at UT Southwestern.
In the NEJM study, patients took one course of teplizumab (14 days’ worth of medication). We anticipate further research to determine whether multiple or longer treatment cycles can safely provide additional years of insulin production, or perhaps prevent the disease entirely. We also expect researchers to investigate combination therapies – teplizumab paired with other treatments – to discover whether we can improve results, reduce side effects, or both.
With advancements like the use of teplizumab, families can move from a mindset that there’s nothing that can be done to prevent T1D to having more control over their health. It’s our goal as health care providers and researchers to one day find a way to prevent Type 1 diabetes altogether.
