This transcript has been edited for clarity.
The US Food and Drug Administration (FDA) has just approved teplizumab (Tzield) for the delay of clinical type 1 diabetes in people age 8 years or older who have stage 2 type 1 diabetes.
Before I talk about teplizumab, I'm going to talk about the stages of type 1 diabetes that we've learned about over the past decade or so. I think it's important to understand these stages so that we can discuss them with our patients.
Stage 1 type 1 diabetes means that someone has beta-cell autoimmunity and normal glucose levels. Beta-cell autoimmunity means that someone has two or more islet autoantibodies present; that means anti-insulin antibodies, GAD65, IA-2, and/or the zinc transporter autoantibodies. All of these are commercially available, so you can measure them in your patients. If they have two or more that are positive and normal glucose levels, they are considered stage 1. These people are presymptomatic. They don't know they are at risk for type 1 diabetes unless you measure their autoantibodies.
Stage 2 type 1 diabetes is really prediabetes in someone who's going to get type 1 diabetes. They have evidence of beta-cell autoimmunity, but now they have dysglycemia and they're presymptomatic. They basically have an impaired fasting glucose level ≥ 100. They have abnormal glucose levels on a glucose tolerance test. Unlike with pre–type 2 diabetes, there are glucose levels at intermediate time points of 30, 60, and 90 minutes that can also make the diagnosis and/or they have an A1c level ≥ 5.7%. These are people who have the autoantibodies, and you see that they have prediabetes.
One of the problems is that we use the same criteria, by and large, that have been developed to look at prediabetes in people with type 2 diabetes. There's ongoing research looking at the optimal values for predicting the rate of progression to the onset of symptomatic type 1 diabetes in these people. Symptomatic type 1 diabetes is considered stage 3.
People with stage 3 type 1 diabetes now fit the glycemic definition of diabetes, and they have the presence of two or more autoantibodies. At stage 2, there is a very high risk that someone is going to go on to develop stage 3 type 1 diabetes. There is a 60% risk that someone will develop overt type 1 diabetes in 2 years and a 75% risk that it will develop over the next 4-5 years. We really want to try to do something with those patients at stage 2 so that they don't go on to develop stage 3 or clinically significant type 1 diabetes.
Teplizumab works to slow the progression from stage 2 type 1 diabetes to stage 3 or clinically significant type 1 diabetes. It is the first approved disease-modifying agent for type 1 diabetes. It demonstrates a median 2-year delay in the progression from stage 2 to stage 3 type 1 diabetes. It is an anti-CD3 monoclonal receptor–nonbinding antibody.
The study used for approval of teplizumab included 76 participants with stage 2 type 1 diabetes; 44 patients were randomized to the teplizumab group and 32 to the placebo group. The drug is given as a daily infusion for 14 consecutive days. Patients were then followed for a median of 51 months.
The time to diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group. The disease was diagnosed in 43% of the participants who received teplizumab vs 72% who received placebo.
Looked at another way, the annualized rates of the diagnosis of stage 3 or clinical type 1 diabetes were about 15% per year in the teplizumab group and approximately 36% per year in the placebo group. This represents a statistically significant delay in the development of stage 3 type 1 diabetes.
There were no unexpected side effects, but they did see adverse events of rash, headache, and transient lymphopenia.
I know we would all love a cure for type 1 diabetes, or at least the ability to completely prevent progression to type 1 diabetes, but teplizumab really opens the door. It's the start for our doing something to help prevent or at least slow the progression to developing stage 3 type 1 diabetes. I think first steps are first steps.
One of the really important factors here lies in how much we will be screening people for pre–type 1 diabetes. I'm interested to see how the American Diabetes Association changes their guidelines now that we have something to give people to slow progression.
I want to see how this really impacts people, particularly children, because I think that for a young child, to develop type 1 diabetes is really overwhelming and requires a great deal of change in their life. If that can be slowed — the progression to needing insulin, needing to poke their fingers, or using an insulin pump — I think all that may be very impactful.
In adults, it will also be impactful, but I think it's important to evaluate each patient and to determine what their needs are and what's best for that person.
This is the first time ever we've been able to slow the progression of type 1 diabetes through the stages. I'm really looking forward to using this agent and seeing how my patients respond.
Anne L. Peters, MD, is a professor of medicine at the University of Southern California (USC) Keck School of Medicine and director of the USC clinical diabetes programs. She has published more than 200 articles, reviews, and abstracts, and three books, on diabetes, and has been an investigator for more than 40 research studies. She has spoken internationally at over 400 programs and serves on many committees of several professional organizations.
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Cite this: Anne L. Peters. New Agent: 'First Step' Toward Delaying Progression of Type 1 Diabetes - Medscape - Nov 22, 2022.
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