Immune-Targeting Drug Improves Insulin Production and Alters Autoimmune Response but Does Not Delay Type 1 Diabetes

A clinical trial testing the immune-targeting drug abatacept in people at high risk of developing type 1 diabetes demonstrated that the drug had beneficial effects on β (beta) cell function but did not delay type 1 diabetes diagnosis. Previous research in people newly diagnosed with type 1 diabetes found that abatacept helped maintain insulin production, possibly by reducing the activation of specific kinds of immune cells and interrupting the misdirected autoimmune attack on β cells. Based on these results, researchers from the Type 1 Diabetes TrialNet tested whether abatacept could delay or prevent progression of the disease at earlier stages. They enrolled 212 men, women, and children ages 6 to 45 years who were relatives of people with type 1 diabetes and had “stage 1” type 1 diabetes. Those with stage 1 diabetes have two or more autoantibodies that indicate early stages of the autoimmune attack but have no clinical symptoms of the disease. Stage 1 eventually progresses to abnormal blood glucose (sugar) levels (stage 2) and then to clinical diagnosis of type 1 diabetes (stage 3). Trial participants were randomly assigned to receive either intravenous infusions of abatacept or a placebo over 12 months. Scientists monitored the participants’ insulin production, ability to maintain healthy blood glucose levels, and development of additional autoantibodies for signs of type 1 diabetes progression. This 1-year course of abatacept treatment did not significantly prevent progression from stage 1 to stage 2 type 1 diabetes, nor did it delay or prevent clinical diagnosis of type 1 diabetes compared to placebo. However, participants who received abatacept showed immune cell changes indicative of an altered autoimmune response and had improved β-cell function and insulin secretion compared to those who received placebo. These effects were not permanent and were lost once the drug was discontinued.

These results provide important new data about the mechanisms and timing of type 1 diabetes progression. Further research is needed to determine if abatacept’s effects on the immune system can help modify type 1 diabetes progression at a different disease stage, in longer treatment courses, or in combination with another therapy.