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


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.
Gottlieb
Peter A
PA
Barbara Davis Center for Childhood Diabetes, University of Colorado at Denver, Aurora, Colorado, USA. peter.gottlieb@ucdenver.edu
Quinlan
Scott
S
Krause-Steinrauf
Heidi
H
Greenbaum
Carla J
CJ
Wilson
Darrell M
DM
Rodriguez
Henry
H
Schatz
Desmond A
DA
Moran
Antoinette M
AM
Lachin
John M
JM
Skyler
Jay S
JS
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002648:Child; D000077561:Daclizumab; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology* / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D000077561:Daclizumab; D009173:Mycophenolic Acid