ADA 2011: New Developments in the Treatment of Type 1 Diabetes

Researchers are investigating novel ways to preserve beta cell function in patients with type 1 diabetes and enhance the body’s ability to produce its own insulin.

Although many of the presentations and posters at the ADA 71st Annual Meeting in San Diego have focused on type 2 diabetes, several researchers have presented information on recent advances in treating type 1 diabetes (T1D). At a press briefing on Sunday, investigators from various research and academic centers presented results from eight studies in various stages of clinical development. The goal of all of the studies is to find drugs that prevent or treat T1D by preserving beta cell function and prolonging the body’s ability to produce its own insulin.

Kevan Herold, MD, lead researcher of the AbATE trial, discussed findings of a phase II randomized controlled trial (RCT) involving 83 participants ages 8-30 years who were newly diagnosed with T1D. The purpose of the study was to determine whether a second course of teplizumab, an anti-CD3 medication which modulates T-cells, would significantly preserve beta cell function. Although results did not show added benefit of the second course, after 2 years, participants in the treatment group showed a 45% decrease in beta cell function compared to a 77% decrease in an untreated group. This study shows promise, as “preserving the body’s own beta cell function is far better than relying on exogenous insulin,” said Herold. The Protégé study is a two-year phase III RCT evaluating whether teplizumab can reduce A1C to less than 6.5% in newly diagnosed T1D patients. Nicole Sherry, MD, reported results from this study of 560 participants. Although findings did not reveal differences between treatment and placebo in the primary outcome of a reduction of insulin, teplizumab did preserve or increase C-peptide levels.

In a phase III study evaluating another anti-CD3 drug, otelixizumab, researchers determined whether administering a much lower dose (3.1 mg) would preserve its efficacy while reducing adverse events seen with the original dose. Co-investigator Peter Gottlieb, MD, of the DEFEND-1 trial, reported that although the drug was safe at the lower dose, it was not effective in preserving C-peptide. “This pathway is clearly one that can work, but the dose that was chosen was too low,” explained Gottlieb. Future trials may be useful in determining the optimal dose to balance efficacy and safety.

DiaPep277 is potential vaccine for T1D currently in phase III. In a phase II study, the goal was to prevent beta cell destruction by removing 24 of 500 amino acids from a “heat shock” protein that exists in beta cells and causes destruction through activation of destructive T-cells. DiaPep277 is this altered heat shock protein, which was administered subcutaneously to 100 newly diagnosed T1D patients. Itamar Raz, MD, presented results showing that DiaPep277 succeeded in protecting beta cells, and this effect lasted up to two years following diagnosis.

A phase II RCT conducted by the type 1 Diabetes TrialNet study group compared abatacept to placebo in newly diagnosed T1D. Jay Skyler, MD, reported findings which showed that patients in the treatment group had 59% higher levels of C-peptide compared to placebo after 2 years. On average, there was a 9.6-month delay, indicating that “this may be a potential component in combination therapy,” said Skyler. Another TrialNet study evaluated the vaccine GAD65, which showed no difference in benefits or side effects between treatment and placebo groups. It has worked in animal studies, so it may just be a matter of different dosing.

Carla Greenbaum, MD, presented findings from a phase I trial of interleukin-2 in combination with rapamycin. This was a study involving two drugs approved for other indications that were never used in combination. The goal was to increase cells that perpetuate the immune response and decrease cells that attack the immune system. Results showed no benefit of the combination on insulin secretion. However, researchers are still investigating this approach.