Antigen-based immunotherapies do not prevent progression of recent-onset autoimmune diabetes: a systematic review and meta-analysis

We performed a systematic review and meta-analysis to assess the efficacy and safety of antigen-based immunotherapies in tertiary prevention of autoimmune diabetes. We searched for randomised controlled trials testing antigen-based immunotherapies in patients with recent-onset type 1 diabetes or latent autoimmune diabetes of adults in MEDLINE, COCHRANE and EMBASE databases, trial registries, conference proceedings and reference lists of pertinent records. Primary outcomes were fasting and stimulated C-peptide (after glucagon or mixed meal stimulation). Change in glycosylated haemoglobin (HbA_1c), daily insulin needs and incidence of any or severe hypoglycaemic events or severe adverse events were secondary outcomes. Fifteen studies were included in the meta-analysis. Overall, there was no difference in fasting [weighted mean difference (WMD) 0.01 nmol/L; 95 % confidence interval (CI) -0.09, 0.11; I ² = 73 %] or mixed meal stimulated C-peptide (WMD 0.02 nmol/L/min; 95 % CI -0.08, 0.12; I ² = 50 %) compared with placebo. Glucagon stimulated C-peptide was maintained higher (WMD 0.13 nmol/L/min; 95 % CI 0.05, 0.21; I ² = 0 %) in patients treated with Diapep277. Moreover, there was no change in daily insulin needs (WMD 0.02 IU/kg; 95 % CI -0.04, 0.09; I ² = 51 %) or HbA_1c (WMD -0.06 %; 95 % CI -0.35, 0.23; I ² = 42 %) vs. placebo. Finally, there was no effect on the incidence of severe hypoglycaemic events or overall serious adverse events [risk ratio 0.94, 95 % CI 0.62, 1.41; I ² = 0 % and 0.87; 95 % CI 0.53, 1.44; I ² = 0 %, respectively). Antigen-based immunotherapies are not effective in preventing the progression of autoimmune diabetes in newly diagnosed patients.