Abstract
AIMS: Residual beta cell function in Type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd(R)) given in three intralymphatic injections with oral Vitamin D has shown promising results in persons with T1D carrying the HLA DR3-DQ2 haplotype in the phase IIb trial DIAGNODE-2.
We aimed to explore the efficacy of intralymphatic GAD-alum on blood glucose recorded by continuous glucose monitoring (CGM). METHODS: DIAGNODE-2 (NCT03345004) was a multicenter, randomized, placebo-controlled, double-blind trial of 109 recent-onset T1D patients aged 12-24 years with GAD65 antibodies and fasting C-peptide >0.12 nmol/L, which randomized patients to three intralymphatic injections of 4 μg GAD-alum and oral Vitamin D, or placebo.
We report results for exploratory endpoints assessed by 14-day CGM at Months 0, 6 and 15. Treatment arms were compared by mixed-effects models for repeated measures adjusting for baseline values.
RESULTS: We included 98 patients with CGM recordings of sufficient quality (DR3-DQ2-positive patients: 27 GAD-alum-treated and 15 placebo-treated). In DR3-DQ2-positive patients, % time in range (TIR, 3.9-10 mmol/L) declined less between baseline and Month 15 in GAD-alum-treated compared to placebo-treated patients (-5.1% and -16.7%, respectively, p=0.0075), with reduced time >13.9 mmol/L (p=0.0036), and significant benefits on the glucose management indicator (p=0.0025).
No differences were detected for hypoglycaemia. GAD-alum compared to placebo lowered the increase in glycaemic variability (standard deviation) observed in both groups (p=0.0219).
Change in C-peptide was correlated with the change in TIR. CONCLUSIONS: Intralymphatic GAD-alum improves glycaemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.