A single course of low-dose antithymocyte globulin (ATG) given within 3 months of clinical diagnosis of type 1 diabetes (T1D) slowed β-cell function decline and reduced hemoglobin A1c level for at least 1 year after therapy, according to findings published in Diabetes Care.
Previously, a pilot study suggested that combination therapy with low-dose ATG and pegylated granulocyte colony-stimulating factor (GCSF) may preserve C-peptide in patients with T1D. In the current study, researchers hypothesized that either combination low-dose ATG/GCSF or low-dose ATG alone would slow the decline of β-cell function in patients with newly diagnosed disease.
A phase 2B triple-arm, randomized, double-masked, placebo-controlled trial was conducted by the Type 1 Diabetes TrialNet Study Group in a cohort that included 89 patients with a recent clinical diagnosis of T1D. Within this group, 29 were randomly assigned to ATG (2.5 mg/kg intravenously) followed by pegylated GCSF (6 mg subcutaneously every 2 weeks for 6 doses), 29 were randomly assigned to ATG alone (2.5 mg/kg), and 31 were randomly assigned to placebo. The study’s primary end point was mean area under the curve (AUC) C-peptide after one year of therapy, during a 2-hour mixed-meal tolerance test.
At one year, the mean AUC C-peptide was significantly higher in those who received ATG (0.646 nmol/L) compared with placebo (0.406 nmol/L) (P =.0003) but the same effect was not observed for those who received ATG/GCSF (0.528 nmol/L) vs placebo (P =.031). Hemoglobin A1c was significantly lower at 1 year in both the ATG and ATG/GCSF cohorts (P =.002 and P =.011, respectively).
“Long-term follow-up of this study cohort will determine the duration of protection afforded by low-dose ATG,” wrote the authors.
Haller MJ, Schatz DA, Skyler JS, et al.; Type 1 Diabetes TrialNet ATG-GCSF Study Group. Low-dose anti-thymocyte globulin (ATG) preserves β-cell function and improves HbA(1c) in new-onset type 1 diabetes [published online July 16, 2018]. Diabetes Care. doi: 10.2337/dc18-0494.