Failure to preserve beta-cell function with mycophenolate mofetil and daclizumab combined therapy in patients with new- onset type 1 diabetes

Abstract

Objective: This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing beta-cells in subjects with new-onset type 1 diabetes.

Research design and methods: A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test.

Results: One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly.

Conclusions: Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process.

Figure 1

Effect of MMF and MMF plus DZB on C-peptide over 2 years. A) The geometric means and 95% CIs for the 2-h AUC stimulated C-peptide levels over time within each group. B) The cumulative incidence of decline in peak C-peptide to <0.2 pmol/ml within each group. The relative hazard was 0.61 (95% CI: 0.28–1.33, P = 0.11) for MMF plus DZB vs. control, and 1.05 (0.50–2.19, P = 0.83) for MMF alone vs. control. C) Ratio of geometric means for MMF plus DZB vs. control groups, with 95% CIs, within subgroups of subjects defined at baseline. D) Likewise for MMF alone vs. control (A1C 2nd tertile upper 95% confidence limit is 28.9).

Figure 2

Effect of MMF and MMF plus DZB on glycemic control over time. A) Mean A1C (%) and 95% confidence limits over time. B) Mean insulin dose and 95% confidence limits over time within each group.