Identification

Name
Dulaglutide
Accession Number
DB09045
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Fusion proteins / Hormones
Description

Dulaglutide is a novel glucagon-like peptide-1 agonist (GLP-1) biologic drug consisting of a dipeptidyl peptidase-IV-protected GLP-1 analogue covalently linked to a human IgG4-Fc heavy chain by a small peptide linker. Dulaglutide is indicated in the treatment of type 2 diabetes and can be used once a week. It was approved by the FDA in September 2014. Dulaglutide is manufactured and marketed by Eli Lily under the brand Trulicity™. It is not known if dulaglutide can increase the risk of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, and is thus not recommended for use in populations with a personal or family history of these conditions.

Protein structure
Db09045
Protein chemical formula
C2646H4044N704O836S18
Protein average weight
59669.81 Da
Sequences
> Dulaglutide Sequence
HGEGTFTSDVSSYLEEQAAKEFIAWLVKGGGGGGGSGGGGSGGGGSAESKYGPPCPPCPA
PEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKP
REEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTL
PPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLT
VDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLG
Download FASTA Format
Synonyms
Not Available
External IDs
LY-2189265
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TrulicitySolution1.5 mgSubcutaneousEli Lilly & Co. Ltd.Not applicableNot applicableCanada
TrulicitySolution0.75 mgSubcutaneousEli Lilly & Co. Ltd.2016-01-08Not applicableCanada
TrulicityInjection, solution0.75 mg/0.5mLSubcutaneousEli Lilly and Company2014-09-18Not applicableUs
TrulicityInjection, solution1.5 mg/0.5mLSubcutaneousEli Lilly Italia SPA2014-11-07Not applicableUs
TrulicitySolution0.75 mgSubcutaneousEli Lilly & Co. Ltd.Not applicableNot applicableCanada
TrulicityInjection, solution0.75 mg/0.5mLSubcutaneousA-S Medication Solutions2014-11-07Not applicableUs
TrulicityInjection, solution0.75 mg/0.5mLSubcutaneousEli Lilly Italia SPA2014-11-07Not applicableUs
TrulicitySolution1.5 mgSubcutaneousEli Lilly & Co. Ltd.2015-11-24Not applicableCanada
TrulicityInjection, solution1.5 mg/0.5mLSubcutaneousEli Lilly and Company2014-09-18Not applicableUs
TrulicityInjection, solution1.5 mg/0.5mLSubcutaneousA-S Medication Solutions2014-11-07Not applicableUs
Categories
UNII
WTT295HSY5
CAS number
923950-08-7

Pharmacology

Indication

Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Associated Conditions
Pharmacodynamics

Dulaglutide activates human glucagon-like peptide-1 receptors, thus increasing intracellular cyclic AMP in beta cells. This, in turn, increases glucose-dependent insulin release. Dulaglutide also reduces glucagon secretion and slows gastric emptying.

Mechanism of action

Dulaglutide is a human GLP-1 receptor agonist with 90% amino acid sequence homology to endogenous human GLP-1 (7-37). Dulaglutide activates the GLP-1 receptor, a membrane-bound cell-surface receptor coupled to adenylyl cyclase in pancreatic beta cells. Dulaglutide increases intracellular cyclic AMP (cAMP) in beta cells leading to glucose-dependent insulin release. Dulaglutide also decreases glucagon secretion and slows gastric emptying.

TargetActionsOrganism
AGlucagon-like peptide 1 receptor
agonist
Human
Absorption

Maximum plasma concentration (Cmax) is achieved in 24–72 h (median 48 h) after a subcutaneous injection administered at a steady state.

Volume of distribution

After subcutaneous administration of 0.75 mg and 1.5 mg to steady state were approximately 19.2 L (range 14.3 to 26.4 L) and 17.4 L (range 9.3 to 33 L), respectively.

Protein binding
Not Available
Metabolism

Dulaglutide is presumed to be degraded into its component amino acids by general protein catabolism pathways.

Route of elimination
Not Available
Half life

Approximately 5 days.

Clearance

The mean apparent clearance at steady state of dulaglutide is approximately 0.111 L/h for the 0.75 mg dose, and 0.107 L/h for the 1.5 mg dose.

Toxicity

-RISK OF THYROID C-CELL TUMORS -Dulaglutide is contraindicated in patients with a personal or family history of MTC or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN2). Routine serum calcitonin or thyroid ultrasound monitoring is of uncertain value in patients treated with Dulaglutide.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Dulaglutide can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Dulaglutide.
AbituzumabThe risk or severity of adverse effects can be increased when Dulaglutide is combined with Abituzumab.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Dulaglutide.
AcetazolamideThe therapeutic efficacy of Dulaglutide can be increased when used in combination with Acetazolamide.
AcetohexamideDulaglutide may increase the hypoglycemic activities of Acetohexamide.
Acetyl sulfisoxazoleThe therapeutic efficacy of Dulaglutide can be increased when used in combination with Acetyl sulfisoxazole.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Dulaglutide.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Dulaglutide.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Dulaglutide.
Food Interactions
Not Available

References

General References
  1. Nadkarni P, Chepurny OG, Holz GG: Regulation of glucose homeostasis by GLP-1. Prog Mol Biol Transl Sci. 2014;121:23-65. doi: 10.1016/B978-0-12-800101-1.00002-8. [PubMed:24373234]
  2. Sanford M: Dulaglutide: first global approval. Drugs. 2014 Nov;74(17):2097-103. doi: 10.1007/s40265-014-0320-7. [PubMed:25367716]
External Links
UniProt
P43220
KEGG Drug
D09889
PubChem Substance
347910397
ChEMBL
CHEMBL2108027
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dulaglutide
ATC Codes
A10BX14 — Dulaglutide
AHFS Codes
  • 68:20.06 — Incretin Mimetics
MSDS
Download (97.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceHealthy Volunteers / Type 2 Diabetes Mellitus1
1CompletedTreatmentHealthy Volunteers / Type 2 Diabetes Mellitus1
1CompletedTreatmentType 2 Diabetes Mellitus8
2CompletedTreatmentThirst / Water-Electrolyte Imbalance1
2CompletedTreatmentType 2 Diabetes Mellitus5
2Not Yet RecruitingTreatmentAdult Subjects With Type1Diabetes and Insulin Microsecretion1
2RecruitingTreatmentCessation, Smoking / Craving / Glucagon-like Peptide-1 / Weight Change, Body1
2RecruitingTreatmentPrimary Polydipsia1
2, 3CompletedTreatmentType 2 Diabetes Mellitus1
3Active Not RecruitingTreatmentType 2 Diabetes Mellitus1
3CompletedTreatmentCardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
3CompletedTreatmentChronic Kidney Disease (CKD) / Type 2 Diabetes Mellitus1
3CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus2
3CompletedTreatmentType 2 Diabetes Mellitus13
3Not Yet RecruitingTreatmentType 2 Diabetes Mellitus1
3RecruitingTreatmentType 2 Diabetes Mellitus2
4Active Not RecruitingTreatmentType 2 Diabetes Mellitus1
4CompletedTreatmentType 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentNASH - Nonalcoholic Steatohepatitis / Type 2 Diabetes Mellitus1
4RecruitingTreatmentType 2 Diabetes Mellitus1
Not AvailableNot Yet RecruitingTreatmentNon Alcoholic Fatty Liver Diseases (NAFLD) / Type2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous0.75 mg/0.5mL
Injection, solutionSubcutaneous1.5 mg/0.5mL
SolutionSubcutaneous0.75 mg
SolutionSubcutaneous1.5 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Transmembrane signaling receptor activity
Specific Function
This is a receptor for glucagon-like peptide 1. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Gene Name
GLP1R
Uniprot ID
P43220
Uniprot Name
Glucagon-like peptide 1 receptor
Molecular Weight
53025.22 Da
References
  1. Sanford M: Dulaglutide: first global approval. Drugs. 2014 Nov;74(17):2097-103. doi: 10.1007/s40265-014-0320-7. [PubMed:25367716]

Drug created on April 29, 2015 12:08 / Updated on October 21, 2018 20:36