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

Abstract

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.

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Authors+Show Affiliations

,

University of Copenhagen, Gentofte Hospital, Department of Internal Medicine F, Niels Andersens Vej 65, 2900 Hellerup, Denmark.

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Source

MeSH

Blood Glucose
C-Peptide
Clinical Trials as Topic
Diabetes Mellitus, Type 2
Gastrointestinal Diseases
Glucagon-Like Peptide 1
Glucagon-Like Peptides
Glycated Hemoglobin A
Humans
Hypoglycemic Agents
Immunoglobulin Fc Fragments
Insulin
Recombinant Fusion Proteins
Treatment Outcome

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21154170

Citation

Jimenez-Solem, Espen, et al. "Dulaglutide, a Long-acting GLP-1 Analog Fused With an Fc Antibody Fragment for the Potential Treatment of Type 2 Diabetes." Current Opinion in Molecular Therapeutics, vol. 12, no. 6, 2010, pp. 790-7.
Jimenez-Solem E, Rasmussen MH, Christensen M, et al. 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;12(6):790-7.
Jimenez-Solem, E., Rasmussen, M. H., Christensen, M., & Knop, F. K. (2010). Dulaglutide, a long-acting GLP-1 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes. Current Opinion in Molecular Therapeutics, 12(6), pp. 790-7.
Jimenez-Solem E, et al. 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;12(6):790-7. PubMed PMID: 21154170.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dulaglutide, a long-acting GLP-1 analog fused with an Fc antibody fragment for the potential treatment of type 2 diabetes. AU - Jimenez-Solem,Espen, AU - Rasmussen,Mette H, AU - Christensen,Mikkel, AU - Knop,Filip K, PY - 2010/12/15/entrez PY - 2010/12/15/pubmed PY - 2011/5/20/medline SP - 790 EP - 7 JF - Current opinion in molecular therapeutics JO - Curr. Opin. Mol. Ther. VL - 12 IS - 6 N2 - 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. SN - 2040-3445 UR - https://www.unboundmedicine.com/medline/citation/21154170/Dulaglutide,_a_long-acting_GLP-1_analog_fused_with_an_Fc_antibody_fragment_for_the_potential_treatment_of_type_2_diabetes L2 - http://www.diseaseinfosearch.org/result/2236 DB - PRIME DP - Unbound Medicine ER -