Two TrialNet Studies Test Effect of Drugs in Slowing Progression of Type 1 Diabetes
Results of two TrialNet studies testing drugs to slow or stop the immune system’s attack on insulin-producing cells in people newly diagnosed with type 1 diabetes were presented at the American Diabetes Association’s (ADA’s) 71st Scientific Sessions in San Diego in June 2011 and simultaneously published online in the Lancet. The studies were conducted by the National Institutes of Health’s international network of researchers, Type 1 Diabetes TrialNet Study Group, led by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Both studies aimed to preserve secretion of insulin, the hormone that controls blood glucose levels. One study tested the drug abatacept, and the other tested a potential vaccine based on a key protein to which autoimmunity is directed—glutamic acid decarboxylase (GAD). When type 1 diabetes is diagnosed, most patients retain a limited ability to make insulin, which is generally lost rapidly over the following 1 to 2 years. All study participants received intensive management of their diabetes during the trial, with a goal of keeping hemoglobin A1c, also called glycated hemoglobin or A1C, levels within current ADA recommendations.
In the first study, abatacept (Orencia), an immune system modulator currently used to treat several inflammatory diseases, was evaluated in 112 people, ages 6 to 36, with newly diagnosed type 1 diabetes. Participants were randomized to receive injections of either abatacept or placebo over 2 years. The group treated with abatacept had a 9.6 month delay in the progression of loss of insulin production. After 2 years, C-peptide, a marker for the production of insulin, was 59 percent higher in the participants treated with abatacept compared with the placebo group. Long-term retention of the ability to make even small amounts of insulin is associated with better glucose control and improved outcomes in diabetes.
In the second study, GAD-alum, an antigen-based therapy aiming to suppress the immune response, was tested in 145 people, ages 3 to 45, with newly diagnosed type 1 diabetes. Participants were randomized into three groups to receive two or three doses of GAD-alum or alum alone over 4 to 12 weeks. During 1 year of treatment, the vaccine showed no evidence of preserving insulin secretion.
Adverse effects were minimal for both drugs, especially among children, who account for the majority of people with type 1 diabetes.
“We learn something important from every study, and we build on everything we learn. Both positive and negative studies help us develop more effective strategies to prevent and treat type 1 diabetes,” said TrialNet Study Group Chair Jay Skyler, M.D., M.A.C.P. “We will continue to follow people in both studies. It is still early, but there is good reason to believe that some of the drugs being developed to alter immune responses, either alone or in combination with other therapies, will lead to treatments that prevent, postpone, or stop progression of type 1 diabetes.”
TrialNet researchers are conducting a series of studies to test ways to prevent or delay progression of type 1 diabetes. At the 2011 ADA meeting, TrialNet researchers announced two ongoing studies aimed at preventing or delaying type 1 diabetes in relatives of people who already have the disease. One trial is testing an experimental drug called teplizumab, another immune system modulator; the other study is testing oral insulin, which may help suppress the immune responses that lead to type 1 diabetes.
Type 1 diabetes appears to involve both genetic risk factors and less understood environmental factors that may interact to initiate the development of diabetes. To identify people at high risk for type 1 diabetes, TrialNet offers free screening for relatives of people with the disease. Screening involves a simple blood test for markers called autoantibodies that often appear years before diabetes develops. Knowing the number and type of markers makes it possible to identify those at different risk levels for developing type 1 diabetes. Among people with a relative with type 1 diabetes, the chances of developing the disease are 15 times greater than for those with no family history. Screening can refine this risk estimate.
More information about these federally funded TrialNet studies can be found as follows:
- abatacept study—www.clinicaltrials.gov/ct2/show/NCT00505375
- GAD-alum study—www.clinicaltrials.gov/ct2/show/NCT00529399
- teplizumab study—www.clinicaltrials.gov/ct2/show/NCT01030861
- oral insulin study—www.clinicaltrials.gov/ct2/show/NCT00419562
Nearly 200 U.S. TrialNet locations offer screening and conduct studies to identify causes of type 1 diabetes and test ways to prevent or delay the disease. To find a TrialNet location or to learn more, visit www.DiabetesTrialNet.org or call 1–800–425–8361.
The NIDDK has easy-to-read booklets and fact sheets about diabetes. For more information or to obtain copies, visit www.diabetes.niddk.nih.gov.
NIH Publication No. 12–4562
Page last updated: December 19, 2011