Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes

Type 1 Diabetes TrialNet ATG-GCSF Study Group, Michael J Haller, Desmond A Schatz, Jay S Skyler, Jeffrey P Krischer, Brian N Bundy, Jessica L Miller, Mark A Atkinson, Dorothy J Becker, David Baidal, Linda A DiMeglio, Stephen E Gitelman, Robin Goland, Peter A Gottlieb, Kevan C Herold, Jennifer B Marks, Antoinette Moran, Henry Rodriguez, William Russell, Darrell M WilsonCarla J Greenbaum, Polly Bingley

Research output: Contribution to journalArticle (Academic Journal)peer-review

94 Citations (Scopus)


OBJECTIVE: A pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized that 1) low-dose ATG/GCSF or 2) low-dose ATG alone would slow the decline of β-cell function in patients with new-onset T1D (duration <100 days).

RESEARCH DESIGN AND METHODS: A three-arm, randomized, double-masked, placebo-controlled trial was performed by the Type 1 Diabetes TrialNet Study Group in 89 subjects: 29 subjects randomized to ATG (2.5 mg/kg intravenously) followed by pegylated GCSF (6 mg subcutaneously every 2 weeks for 6 doses), 29 to ATG alone (2.5 mg/kg), and 31 to placebo. The primary end point was mean area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test 1 year after initiation of therapy. Significance was defined as one-sided P value < 0.025.

RESULTS: The 1-year mean AUC C-peptide was significantly higher in subjects treated with ATG (0.646 nmol/L) versus placebo (0.406 nmol/L) (P = 0.0003) but not in those treated with ATG/GCSF (0.528 nmol/L) versus placebo (P = 0.031). HbA1c was significantly reduced at 1 year in subjects treated with ATG and ATG/GCSF, P = 0.002 and 0.011, respectively.

CONCLUSIONS: Low-dose ATG slowed decline of C-peptide and reduced HbA1c in new-onset T1D. Addition of GCSF did not enhance C-peptide preservation afforded by low-dose ATG. Future studies should be considered to determine whether low-dose ATG alone or in combination with other agents may prevent or delay the onset of the disease.

Original languageEnglish
Pages (from-to)1917-1925
Number of pages9
JournalDiabetes Care
Issue number9
Publication statusPublished - 1 Sept 2018

Bibliographical note

© 2018 by the American Diabetes Association.


  • Adolescent
  • Adult
  • Antilymphocyte Serum/administration & dosage
  • C-Peptide/blood
  • Child
  • Cytoprotection/drug effects
  • Diabetes Mellitus, Type 1/drug therapy
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin A/drug effects
  • Granulocyte Colony-Stimulating Factor/administration & dosage
  • Humans
  • Insulin-Secreting Cells/drug effects
  • Male
  • Pilot Projects
  • Polyethylene Glycols/administration & dosage
  • Recombinant Proteins/administration & dosage
  • Young Adult


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