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

Diabetes Obes Metab. 2016 May;18(5):533-6. doi: 10.1111/dom.12640. Epub 2016 Mar 4.

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.

Keywords: anti-drug antibody; dulaglutide; type 2 diabetes.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / analysis*
  • Antibodies, Neutralizing / isolation & purification
  • Cross Reactions
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / immunology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Eruptions / complications
  • Drug Eruptions / epidemiology
  • Drug Eruptions / physiopathology
  • Drug Hypersensitivity / complications*
  • Drug Hypersensitivity / epidemiology
  • Drug Hypersensitivity / physiopathology
  • Drugs, Investigational / administration & dosage
  • Drugs, Investigational / adverse effects*
  • Drugs, Investigational / therapeutic use
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / antagonists & inhibitors
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucagon-Like Peptides / administration & dosage
  • Glucagon-Like Peptides / adverse effects
  • Glucagon-Like Peptides / analogs & derivatives*
  • Glucagon-Like Peptides / therapeutic use
  • Humans
  • Hyperglycemia / chemically induced
  • Hyperglycemia / prevention & control
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Hypoglycemic Agents / therapeutic use
  • Immunoglobulin Fc Fragments / administration & dosage
  • Immunoglobulin Fc Fragments / adverse effects*
  • Immunoglobulin Fc Fragments / therapeutic use
  • Incidence
  • Injections, Subcutaneous
  • Middle Aged
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / adverse effects*
  • Recombinant Fusion Proteins / therapeutic use
  • Risk
  • Severity of Illness Index
  • Solid Phase Extraction

Substances

  • Antibodies, Neutralizing
  • Drugs, Investigational
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • Glucagon-Like Peptides
  • dulaglutide