title: Antigen-based immunotherapies do not prevent progression of recent-onset autoimmune diabetes: a systematic review and meta-analysis.
abstract: 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 (HbA1c), 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; I2= 73 %] or mixed meal stimulated C-peptide (WMD 0.02 nmol/L/min; 95 % CI -0.08, 0.12; I2= 50 %) compared with placebo. Glucagon stimulated C-peptide was maintained higher (WMD 0.13 nmol/L/min; 95 % CI 0.05, 0.21; I2= 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; I2= 51 %) or HbA1c(WMD -0.06 %; 95 % CI -0.35, 0.23; I2= 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; I2= 0 % and 0.87; 95 % CI 0.53, 1.44; I2= 0 %, respectively). Antigen-based immunotherapies are not effective in preventing the progression of autoimmune diabetes in newly diagnosed patients.
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Rizava
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Aristotle University Thessaloniki, Thessaloniki, Greece.|Diabetes Centre, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Bekiari
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: Aris
authors.initials: A
authors.lastname: Liakos
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Sarigianni
authors.affiliation: Diabetes Centre, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Rika
authors.affiliation: Department of Hygiene and Epidemiology, School of Health Sciences, Department of Medicine, Aristotle University Thessaloniki, Thessaloniki, 54124, Greece.
authors.forename: Anna Bettina
authors.initials: AB
authors.lastname: Haidich
authors.affiliation: Fourth Paediatric Department, Aristotle University Thessaloniki, Thessaloniki, Greece.
authors.forename: Asimina
authors.initials: A
authors.lastname: Galli-Tsinopoulou
authors.affiliation: Clinical Research and Evidence-Based Medicine Unit, Aristotle University Thessaloniki, Thessaloniki, Greece. atsapas@auth.gr.|Diabetes Centre, Second Medical Department, Aristotle University Thessaloniki, Thessaloniki, Greece. atsapas@auth.gr.|Harris Manchester College, University of Oxford, Oxford, UK. atsapas@auth.gr.
authors.forename: Apostolos
authors.initials: A
authors.lastname: Tsapas
mesh_terms: D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000628:therapy*; D005934:Glucagon; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007167:Immunotherapy; D007328:Insulin / Q000008:administration & dosage; D012044:Regression Analysis
chemical_list: D002096:C-Peptide; D005934:Glucagon; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human
keywords: Chaperonin 60; Diabetes, Autoimmune; Glutamate decarboxylase; Immunotherapy; Insulin; Tertiary prevention