Dulaglutide, a long-acting GLP-1 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes

Curr Opin Mol Ther. 2010 Dec;12(6):790-7.


Dulaglutide (LY-2189265) is a novel, long-acting glucagon-like peptide 1 (GLP-1) analog being developed by Eli Lilly for the treatment of type 2 diabetes mellitus (T2DM). Dulaglutide consists of GLP-1(7-37) covalently linked to an Fc fragment of human IgG4, thereby protecting the GLP-1 moiety from inactivation by dipeptidyl peptidase 4. In vitro and in vivo studies on T2DM models demonstrated glucose-dependent insulin secretion stimulation. Pharmacokinetic studies demonstrated a t1/2 in humans of up to 90 h, making dulaglutide an ideal candidate for once-weekly dosing. Clinical trials suggest that dulaglutide reduces plasma glucose, and has an insulinotropic effect increasing insulin and C-peptide levels. Two phase II clinical trials demonstrated a dose-dependent reduction in glycated hemoglobin (HbA1c) of up to 1.52% compared with placebo. Side effects associated with dulaglutide administration were mainly gastrointestinal. To date, there have been no reports on the formation of antibodies against dulaglutide, but, clearly, long-term data will be needed to asses this and other possible side effects. The results of several phase III clinical trials are awaited for clarification of the expected effects on HbA1c and body weight. If dulaglutide possesses similar efficacy to other GLP-1 analogs, the once-weekly treatment will most likely be welcomed by patients with T2DM.

MeSH terms

  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Gastrointestinal Diseases / chemically induced
  • Glucagon-Like Peptide 1 / genetics
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptides / analogs & derivatives
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use*
  • Immunoglobulin Fc Fragments / adverse effects
  • Immunoglobulin Fc Fragments / genetics
  • Immunoglobulin Fc Fragments / metabolism
  • Immunoglobulin Fc Fragments / therapeutic use*
  • Insulin / blood
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Fusion Proteins / pharmacokinetics
  • Recombinant Fusion Proteins / therapeutic use*
  • Treatment Outcome


  • Blood Glucose
  • C-Peptide
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Insulin
  • Recombinant Fusion Proteins
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • dulaglutide