PMID- 26847401
OWN - NLM
STAT- MEDLINE
DCOM- 20170106
LR  - 20170107
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 18
IP  - 5
DP  - 2016 May
TI  - Low incidence of anti-drug antibodies in patients with type 2 diabetes treated 
      with once-weekly glucagon-like peptide-1 receptor agonist dulaglutide.
PG  - 533-6
LID - 10.1111/dom.12640 [doi]
AB  - 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.
CI  - (c) 2016 John Wiley & Sons Ltd.
FAU - Milicevic, Z
AU  - Milicevic Z
AD  - Eli Lilly and Company, Vienna, Austria.
FAU - Anglin, G
AU  - Anglin G
AD  - Eli Lilly Canada Inc., Toronto, ON, Canada.
FAU - Harper, K
AU  - Harper K
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Konrad, R J
AU  - Konrad RJ
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Skrivanek, Z
AU  - Skrivanek Z
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Glaesner, W
AU  - Glaesner W
AD  - Eli Lilly and Company, San Diego, CA, USA.
FAU - Karanikas, C A
AU  - Karanikas CA
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
FAU - Mace, K
AU  - Mace K
AD  - Eli Lilly and Company, Indianapolis, IN, USA.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160304
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Drugs, Investigational)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Immunoglobulin Fc Fragments)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 62340-29-8 (Glucagon-Like Peptides)
RN  - WTT295HSY5 (dulaglutide)
SB  - IM
MH  - Antibodies, Neutralizing/*analysis/isolation & purification
MH  - Cross Reactions
MH  - Diabetes Mellitus, Type 2/blood/*complications/drug therapy/immunology
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Drug Eruptions/complications/epidemiology/physiopathology
MH  - Drug Hypersensitivity/*complications/epidemiology/physiopathology
MH  - Drugs, Investigational/administration & dosage/*adverse effects/therapeutic use
MH  - Glucagon-Like Peptide-1 Receptor/*agonists/antagonists & inhibitors/metabolism
MH  - Glucagon-Like Peptides/administration & dosage/adverse effects/*analogs & 
      derivatives/therapeutic use
MH  - Humans
MH  - Hyperglycemia/chemically induced/prevention & control
MH  - Hypoglycemia/prevention & control
MH  - Hypoglycemic Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Immunoglobulin Fc Fragments/administration & dosage/*adverse effects/therapeutic 
      use
MH  - Incidence
MH  - Injections, Subcutaneous
MH  - Middle Aged
MH  - Recombinant Fusion Proteins/administration & dosage/*adverse effects/therapeutic 
      use
MH  - Risk
MH  - Severity of Illness Index
MH  - Solid Phase Extraction
OTO - NOTNLM
OT  - anti-drug antibody
OT  - dulaglutide
OT  - type 2 diabetes
EDAT- 2016/02/06 06:00
MHDA- 2017/01/07 06:00
CRDT- 2016/02/06 06:00
PHST- 2015/11/30 00:00 [received]
PHST- 2016/01/29 00:00 [revised]
PHST- 2016/02/02 00:00 [accepted]
PHST- 2016/02/06 06:00 [entrez]
PHST- 2016/02/06 06:00 [pubmed]
PHST- 2017/01/07 06:00 [medline]
AID - 10.1111/dom.12640 [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2016 May;18(5):533-6. doi: 10.1111/dom.12640. Epub 2016 Mar 
      4.