Background and Aims

Residual beta cell function is crucial for prevention of complications. Most immune interventions have failed with minimal efficacy and/or unacceptable risks. GAD-alum (Diamyd^®) in combination with Vitamin D has shown promising results in Type 1 diabetes (T1D) patients carrying HLA DR3-DQ2.

We aimed to further explore the efficacy of intralymphatic GAD-alum (Diamyd^®) therapy combined with vitamin D on blood glucose recorded by continuous glucose monitoring (CGM) in individuals with recent-onset T1D carrying HLA DR3-DQ2.

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 either three intralymphatic injections of 4 μg GAD-alum and oral vitamin D, or placebo. 14-day CGM recording at Month 0, 6 and 15 were obtained. 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 (27 Diamyd-treated and 15 placebo-treated DR3-DQ2-positive patients) with a median (mean) recording length of 14 (13) days. In DR3-DQ2-positive patients, % time in range (3.9-10 mmol/L; 70-180 mg/dL) declined less between baseline and Month 15 in Diamyd-treated compared to placebo-treated patients (-5.1% and -16.7%, respectively, P =.0075), with reduced time (P=.0036) and number of excursions (P=.0072) above 13.9 mmol/L (250 mg/dL), and better glucose management indicator (GMI, P=.0025). GMI correlated strongly with HbA1c after 6 months.

Conclusions

Intralymphatic GAD-alum (Diamyd®) improves glycemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.