GAD vaccine reduces insulin loss in recently diagnosed type 1 diabetes: findings from a Bayesian meta-analysis

Abstract

Aims/hypothesis: GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. Methods: In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine). Results: We estimate that there is a 98% probability that 20 μg GAD with alum administered twice yields a positive biological effect. The effect is probably a 15–20% reduction in the loss of C-peptide at approximately 1 year after treatment. This translates to an annual expected loss of between −0.250 and −0.235 pmol/ml in treated patients compared with an expected 2 h AUC loss of −0.294 pmol/ml at 1 year for untreated newly diagnosed patients. Conclusions/interpretation: The biological effect of this vaccination should be developed further in order to reach clinically desirable reductions in insulin loss in patients recently diagnosed with type 1 diabetes.