TrialNet Research Leads to FDA Approval of First Drug to Delay Type 1 Diabetes


Landmark findings from TrialNet research were instrumental in the Food and Drug Administration’s (FDA) November 17, 2022, approval of the first drug to delay type 1 diabetes (T1D) in people at risk.

TrialNet conducted the clinical study that discovered the immunotherapy drug teplizumab could delay T1D for 2+ years.

To develop this study, TrialNet collected data from more than 200,000 relatives of people with T1D over the past 20 years. This led to the development of the stages of type 1 diabetes, making it possible to identify who will develop T1D and move prevention research forward.

TrialNet Chair Kevan C. Herold, M.D., Yale University, served as TrialNet Principal Investigator for the study that spanned 10 years.

“We want to thank TrialNet research teams and participants in the Teplizumab Prevention Study and everyone who has participated in T1D research,” said Dr. Herold. “With your help, we are one step closer to a future without T1D.”

Study participants were relatives of people with T1D who had two or more diabetes-related autoantibodies and abnormal blood sugar levels, as identified by TrialNet screening. These individuals are thought to have a lifetime risk of clinical diagnosis nearing 100%. Of the 76 high-risk individuals who participated in the study, 55 were under age 18.

“We will build on this landmark success by continuing to study and identify new ways to slow and eventually stop T1D,” said Dr. Herold. “This accomplishment opens the door to prioritize development of new therapies for slowing and stopping T1D.”

Similar to other autoimmune diseases, such as rheumatoid arthritis, more than one drug may be needed to delay or prevent T1D in everyone. TrialNet is aiming to find other drugs and combinations that work best to offer them to all people who are at risk for T1D.

TrialNet currently has several studies at various stages, including:

The STOP-T1D Prevention Study is scheduled to open for enrollment in early 2023. This study will test a low dose of the immunotherapy drug anti-thymocyte globulin (ATG) to see if it can delay or prevent T1D in people ages 12-35 who have a 50% risk of clinical diagnosis (stage 3) within 2 years. Risk is defined by having two or more diabetes-related autoantibodies and abnormal blood sugar levels (stage 2 T1D) and at least one high-risk marker (based on test results).

TrialNet’s TOPPLE Study is currently testing the safety of a new plasmid therapy in adults diagnosed with T1D in the past 48 months. If this study results in no safety concerns, TrialNet hopes to conduct larger studies to see if this same treatment can slow down or stop T1D in people at risk.

In addition, TrialNet thanks the more than 400 people who took part in TrialNet’s Abatacept Prevention Study and Hydroxychloroquine (HCQ) Prevention Study. Results for these studies will be reported in 2023.

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Study Details Completed

Previous clinical studies have shown the benefit of teplizumab in prolonging insulin production in people recently diagnosed with T1D.

This is the first study to test teplizumab’s ability to delay or prevent disease progression in those at high risk for developing T1D.

All study participants had two or more T1D autoantibodies and abnormal blood sugar levels (Stage 2 T1D) prior to enrollment, as identified by TrialNet Pathway to Prevention risk screening. Individuals in Stage 2 have a lifetime risk of clinical diagnosis (Stage 3 T1D) nearing 100%.

Researchers enrolled 76 people between the ages of 8 and 49; 55 were under age 18. All participants had at least one relative with type 1 diabetes.

Participants were randomly assigned to either the treatment group, which received a 14-day course of teplizumab, or the control group, which received a placebo. All participants regularly underwent oral glucose tolerance tests either until the study was completed or until they developed clinical type 1 diabetes.

Key Findings

  • This is the first study to show any drug can delay type 1 diabetes diagnosis a median of 2 years in adults and children at high risk.
  • 72% of people in the control group developed clinical diabetes, compared to only 43% of the teplizumab group.
  • The median time for people in the control group to develop clinical diabetes (stage 3) was just over 24 months, while those in the treatment group had an average of 48 months before progressing to clinical diabetes (stage 3).
  • Researchers observed, as with other trials involving teplizumab, short-term side effects of rash and low white blood cell counts.
  • Subgroups of individuals may have had a better response to therapy than others.

Next Steps

  • In addition to being able to accurately predict who is going to develop T1D, TrialNet has now found a way to delay it. This is an incredible advancement that gets us one step closer to our ultimate goal: a future without T1D.
  • We know immunotherapy can slow the progression T1D, and we now hope to conduct additional studies to look for ways to extend the benefits of teplizumab, while continuing to test other immune therapies.
  • Samples collected during the Teplizumab Prevention Study are being studied to help researchers understand why some group of individuals had a better response to therapy than others.
  • In addition, TrialNet is conducting extended follow up with participants electing to continue being tested every 6 months.  
  • The latest findings, published in Science Translational Medicine on March 3, 2021, show ongoing delay in diabetes in the teplizumab group. The median time to diabetes diagnosis in the teplizumab group was approximately 60 months (5 years), vs. approximately 27 months (2.3 years) in the placebo group.  
  • In addition to having even more pronounced disease delay, those treated with teplizumab showed improved rates of insulin production. Participants receiving a placebo continued to show a decline in insulin production consistent with disease advancement. 
  • TrialNet will continue testing participants every 6 months, so we can continue to track and report changes. Our hope is that disease delay will extend even further over time. 

In addition, TrialNet is continually planning and launching new studies. As always, we encourage family members of people with T1D to get screened through the Pathway to Prevention Study.

For Study Participants

A big thank you to our amazing participants who made this research possible! Teplizumab participant resources are available here.