A phase III European study results show that Autoantigen treatment of new-onset type 1 diabetes was unsuccessful in preserving pancreatic beta-cell function overall; nevertheless the treatment had some positive effect in certain pre specified patient subgroups.

Patients who were given the autoantigen glutamic acid decarboxylase (GAD) had similar declines in insulin secretion as measured by stimulated C-peptide levels as did patients who were given placebo, with an estimated treatment ratio of 1.16 (95% CI 0.97 to 1.40, P=0.10), according to Johnny Ludvigsson, MD, PhD, from Linköping University in Linköping, Sweden, and colleagues. Males, however, had a 41% greater preservation of C-peptide, with an estimated treatment ratio of 1.41 (95% CI 1.09 to 1.83, P=0.01), the researchers reported in the Feb. 2 New England Journal of Medicine.

The result supports the concept that GAD can be used to preserve residual insulin secretion, although we need to learn more about dosing, intervals, and which groups of patients will have the best effect.

In a previous study by Ludvigsson's group conducted in 70 patients found that treatment with the 65-kD isoform of GAD preserved fasting C-peptide levels for more than two years and stimulated levels for 15 months, indicating residual insulin secretion.
So they conducted a nine-country randomized trial that enrolled 327 patients ages 10 to 20 within three months of being diagnosed with type 1 diabetes.
Patients in the two active treatment groups showed increases in levels of GAD autoantibodies by three months that were significantly higher than in the placebo group (P<0.001). As with the primary endpoint of stimulated C-peptide levels at 15 months, there were no significant differences compared with placebo on various secondary endpoints, including change in fasting C-peptide (P=0.07), change in daily insulin dose (P=0.57), and change in glycated hemoglobin (P=0.86).

In discussing why the results of this study contradicted those seen in the earlier trial, the investigators explained that there may have been differences in the study population or in participating clinicians' traditional treatment approaches. In addition, the treatment groups included more patients ages 10 and 11, while the placebo group included greater numbers of 16-to-20 year olds.