title: Low incidence of anti-drug antibodies in patients with type 2 diabetes treated with once-weekly glucagon-like peptide-1 receptor agonist dulaglutide.
abstract: 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.
authors: Eli Lilly and Company, Vienna, Austria.
authors: Z
authors: Z
authors: Milicevic
authors: Eli Lilly Canada Inc., Toronto, ON, Canada.
authors: G
authors: G
authors: Anglin
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: K
authors: K
authors: Harper
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: R J
authors: RJ
authors: Konrad
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: Z
authors: Z
authors: Skrivanek
authors: Eli Lilly and Company, San Diego, CA, USA.
authors: W
authors: W
authors: Glaesner
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: C A
authors: CA
authors: Karanikas
authors: Eli Lilly and Company, Indianapolis, IN, USA.
authors: K
authors: K
authors: Mace
mesh_terms: D057134:Antibodies, Neutralizing / Q000032:analysis* / Q000302:isolation & purification; D003429:Cross Reactions; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000150:complications / Q000453:epidemiology / Q000503:physiopathology; D004342:Drug Hypersensitivity / Q000150:complications* / Q000453:epidemiology / Q000503:physiopathology; D015507:Drugs, Investigational / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000517:prevention & control; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D007279:Injections, Subcutaneous; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012306:Risk; D012720:Severity of Illness Index; D052616:Solid Phase Extraction; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D057134:Antibodies, Neutralizing; D015507:Drugs, Investigational; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; D004763:Glucagon-Like Peptides; C555680:dulaglutide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: anti-drug antibody; dulaglutide; type 2 diabetes