Low incidence of anti-drug antibodies in patients with type 2 diabetes treated with once-weekly glucagon-like peptide-1 receptor agonist dulaglutide

Therapeutic administration of peptides may result in anti‐drug antibody ( ADA ) formation, hypersensitivity adverse events ( AEs ) and reduced efficacy. As a large peptide, the immunogenicity of once‐weekly glucagon‐like peptide‐1 ( GLP ‐1) receptor agonist dulaglutide is of considerable interest. The present study assessed the incidence of treatment‐emergent dulaglutide ADAs , hypersensitivity AEs , injection site reactions ( ISRs ), and glycaemic control in ADA ‐positive patients in nine phase II and phase III trials (dulaglutide, N = 4006; exenatide, N = 276; non‐ GLP ‐1 comparators, N = 1141). Treatment‐emergent dulaglutide ADAs were detected using a solid‐phase extraction acid dissociation binding assay. Neutralizing ADAs were detected using a cell‐based assay derived from human endothelial kidney cells ( HEK293 ). A total of 64 dulaglutide‐treated patients (1.6% of the population) tested ADA ‐positive versus eight (0.7%) from the non‐ GLP ‐1 comparator group. Of these 64 patients, 34 (0.9%) had dulaglutide‐neutralizing ADAs , 36 (0.9%) had native‐sequence GLP ‐1 ( nsGLP ‐1) cross‐reactive ADAs and four (0.1%) had nsGLP ‐1 neutralization ADAs . The incidence of hypersensitivity AEs and ISRs was similar in the dulaglutide versus placebo groups. No dulaglutide ADA ‐positive patient reported hypersensitivity AEs . Because of the low incidence of ADAs , it was not possible to establish their effect on glycaemic control.