Drug/Small Molecule:
gliclazide

last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for gliclazide and CYP2C9

Summary

There are currently no dosing recommendations for gliclazide based on CYP2C9 genotype.

Annotation

Genotype Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
CYP2C9 *1/*2 None Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (NS) Kinetic effect (NS)
CYP2C9 *2/*2 None Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (NS) Kinetic effect (NS)
CYP2C9 *1/*3 None Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (NS) Kinetic effect (NS)
CYP2C9 *2/*3 None Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (NS) Kinetic effect (NS)
CYP2C9 *3/*3 None Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (NS) Kinetic effect (NS)
  • *See Methods or PMID: 18253145 for definition of "moderate" quality.
  • S: statistically significant difference.
  • NS: non-significant

PharmGKB has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA CYP2C9 *1 N/A N/A N/A
No VIP available No VIP available VA CYP2C9 *2 N/A N/A N/A
No VIP available No VIP available VA CYP2C9 *3 N/A N/A N/A
No VIP available No Clinical Annotations available VA
rs1057910 1075A>C, 47545517A>C, 47639A>C, 96741053A>C, CYP2C9*3, CYP2C9*3:Ile359Leu, CYP2C9: I359L, CYP2C9:359Ile>Leu, CYP2C9:Ile359Leu, Ile359Leu, mRNA 11A>C
A > C
Missense
Ile359Leu
No VIP available No Clinical Annotations available VA
rs1799853 430C>T, 47506511C>T, 8633C>T, 96702047C>T, Arg144Cys, CYP2C9*2, CYP2C9:144Arg>Cys, CYP2C9:Arg144Cys, mRNA 455C>T
C > T
Missense
Arg144Cys
No VIP available No Clinical Annotations available VA
rs5215 1009G>A, 17348630C>T, 17408630C>T, 6577G>A, 748G>A, Val250Ile, Val337Ile
C > T
Missense
Val250Ile
No VIP available CA VA
rs5219 -16-179A>G, 17349572T>C, 17409572T>C, 5635A>G, 67A>G, E23K, KCNJ11: Lys23Glu, KCNJ11:67A>G, KCNJ11:E23K, Lys23Glu
T > C
Intronic
Lys23Glu
No VIP available No Clinical Annotations available VA
rs757110 17358477C>A, 17418477C>A, 4105G>T, 84973G>T, Ala1369Ser
C > A
Missense
Ala1369Ser
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • 1-(3-Azabicyclo(3.3.0)oct-3-yl)-3-(p-tolylsulfonyl)urea
  • 1-(Hexahydrocyclopenta(c)pyrrol-2(1H)-yl)-3-(p-tolylsulfonyl)urea
  • Gliclazida [INN-Spanish]
  • Gliclazidum [INN-Latin]
  • N-(4-Methylbenzenesulfonyl)-N'-(3-azabicyclo(3.3.0)oct-3-yl)urea
Trade Names
  • Diamicron
  • Diamicron MR
  • Glimicron
  • Mylan-Gliclazide
  • Nordialex
  • PMS-Gliclazide
Brand Mixture Names

PharmGKB Accession Id:
PA10892

Description

Gliclazide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the sulfonylurea class of insulin secretagogues, which act by stimulating beta cells of the pancreas to release insulin. Sulfonylureas increase both basal insulin secretion and meal-stimulated insulin release. Medications in this class differ in their dose, rate of absorption, duration of action, route of elimination and binding site on their target pancreatic beta cell receptor. Sulfonylureas also increase peripheral glucose utilization, decrease hepatic gluconeogenesis and may increase the number and sensitivity of insulin receptors. Sulfonylureas are associated with weight gain, though less so than insulin. Due to their mechanism of action, sulfonylureas may cause hypoglycemia and require consistent food intake to decrease this risk. The risk of hypoglycemia is increased in elderly, debilitated and malnourished individuals. Gliclazide has been shown to decrease fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels (reflective of the last 8-10 weeks of glucose control). Gliclazide is extensively metabolized by the liver; its metabolites are excreted in both urine (60-70%) and feces (10-20%).

Source: Drug Bank

Indication

For the treatment of NIDDM in conjunction with diet and exercise.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Gliclazide binds to the beta cell sulfonyl urea receptor (SUR1). This binding subsequently blocks the ATP sensitive potassium channels. The binding results in closure of the channels and leads to a resulting decrease in potassium efflux leads to depolarization of the beta cells. This opens voltage-dependent calcium channels in the beta cell resulting in calmodulin activation, which in turn leads to exocytosis of insulin containing secretorty granules.

Source: Drug Bank

Pharmacology

Gliclazide is a second generation sulphonylurea which acts as a hypoglycemic agent. It stimulates beta cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall, it potentiates insulin release and improves insulin dynamics.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Take without regard to meals. A consistent diet is recommended to reduce the risk of hypoglycemia.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Extensively metabolized in the liver. Less than 1% of the orally administered dose appears unchanged in the urine. Metabolites include oxidized and hydroxylated derivates, as well as glucuronic acid conjugates.

Source: Drug Bank

Protein Binding

94%, highly bound to plasma proteins

Source: Drug Bank

Absorption

Rapidly and well absorbed but may have wide inter- and intra-individual variability. Peak plasma concentrations occur within 4-6 hours of oral administration.

Source: Drug Bank

Half-Life

10.4 hours. Duration of action is 10-24 hours.

Source: Drug Bank

Toxicity

LD 50=3000 mg/kg (orally in mice). Gliclazide and its metabolites may accumulate in those with severe hepatic and/or renal dysfunction. Symptoms of hypoglycemia include: dizziness, lack of energy, drowsiness, headache and sweating.

Source: Drug Bank

Route of Elimination

Metabolites and conjugates are eliminated primarily by the kidneys (60-70%) and also in the feces (10-20%).

Source: Drug Bank

Chemical Properties

Chemical Formula

C15H21N3O3S

Source: Drug Bank

Isomeric SMILES

CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN2C[C@H]3CCC[C@H]3C2

Source: Drug Bank

CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CC2CCCC2C1

Source: Drug Bank

Canonical SMILES

CC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CC2CCCC2C1

Source: Drug Bank

Average Molecular Weight

323.411

Source: Drug Bank

Monoisotopic Molecular Weight

323.130362243

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
ABCC8
DG No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
CYP2C9
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
KCNJ11

Drug Targets

Gene Description
ABCC8 (source: Drug Bank)
ALB (source: Drug Bank)
KCNJ1 (source: Drug Bank)
VEGFA (source: Drug Bank)

Drug Interactions

Drug Description
gliclazide Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemia (source: Drug Bank)
gliclazide Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia. (source: Drug Bank)
gliclazide The salicylate increases the effect of sulfonylurea (source: Drug Bank)
gliclazide Acetylsalicylic acid increases the effect of the sulfonylurea, gliclazide. (source: Drug Bank)
gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide The beta-blocker, atenolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
gliclazide The agent increases the effect of sulfonylurea (source: Drug Bank)
gliclazide The agent increases the effect of sulfonylurea (source: Drug Bank)
gliclazide The agent increases the effect of sulfonylurea (source: Drug Bank)
gliclazide The agent increases the effect of sulfonylurea (source: Drug Bank)
gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide The beta-blocker, esmolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
acebutolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
acebutolol The beta-blocker, acebutolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
aspirin The salicylate increases the effect of sulfonylurea (source: Drug Bank)
atenolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
betaxolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
betaxolol The beta-blocker, betaxolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
bevantolol The beta-blocker, bevantolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
bisoprolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carteolol The beta-blocker, carteolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
chloramphenicol The agent increases the effect of sulfonylurea (source: Drug Bank)
chloramphenicol The agent increases the effect of sulfonylurea (source: Drug Bank)
clofibrate The agent increases the effect of sulfonylurea (source: Drug Bank)
clofibrate The agent increases the effect of sulfonylurea (source: Drug Bank)
dicumarol The agent increases the effect of sulfonylurea (source: Drug Bank)
dicumarol The agent increases the effect of sulfonylurea (source: Drug Bank)
esmolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
glucosamine Possible hyperglycemia (source: Drug Bank)
isocarboxazid The MAO inhibitor increases the effect of the hypoglycemic agent (source: Drug Bank)
labetalol The beta-blocker, labetolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
metoprolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
metoprolol The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
nadolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
nadolol The beta-blocker, nadolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
oxprenolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
oxprenolol The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
penbutolol The beta-blocker, penbutolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
phenelzine The MAO inhibitor increases the effect of the hypoglycemic agent (source: Drug Bank)
phenylbutazone Phenylbutazone increases the effect of the hypoglycemic agent (source: Drug Bank)
phenylbutazone Phenylbutazone increases the effect of the hypoglycemic agent (source: Drug Bank)
pindolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
practolol The beta-blocker, practolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
propranolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
repaglinide Similar mode of action - questionable association (source: Drug Bank)
rifampin Rifampin decreases the effect of sulfonylurea (source: Drug Bank)
rifampin Rifampin decreases the effect of sulfonylurea (source: Drug Bank)
salicylate-magnesium The salicylate increases the effect of sulfonylurea (source: Drug Bank)
salicylate-sodium The salicylate increases the effect of sulfonylurea (source: Drug Bank)
salicylate-sodium The salicylate, salicylate-sodium, increases the effect of the sulfonylurea, gliclazide. (source: Drug Bank)
salsalate The salicylate, salsalate, increases the effect of the sulfonylurea, gliclazide. (source: Drug Bank)
somatropin recombinant Somatropin may antagonize the hypoglycemic effect of gliclazide. Monitor for changes in fasting and postprandial blood sugars. (source: Drug Bank)
sotalol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
sotalol The beta-blocker, sotalol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
timolol The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
tranylcypromine The MAO inhibitor increases the effect of the hypoglycemic agent (source: Drug Bank)
trisalicylate-choline The salicylate, trisalicylate-choline, increases the effect of the sulfonylurea, gliclazide. (source: Drug Bank)
gliclazide The MAO inhibitor increases the effect of hypoglycemic agent (source: Drug Bank)
gliclazide The beta-blocker, labetalol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide The beta-blocker, nadolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
gliclazide The MAO inhibitor increases the effect of the hypoglycemic agent (source: Drug Bank)
gliclazide Phenylbutazone increases the effect of the hypoglycemic agent (source: Drug Bank)
gliclazide Phenylbutazone increases the effect of the hypoglycemic agent (source: Drug Bank)
gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide The beta-blocker, pindolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide The beta-blocker, propranolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
gliclazide Similar mode of action - questionable association (source: Drug Bank)
gliclazide Rifampin decreases the effect of sulfonylurea (source: Drug Bank)
gliclazide Rifampin decreases the effect of sulfonylurea (source: Drug Bank)
gliclazide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
gliclazide The beta-blocker, timolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)

Curated Information ?

Publications related to gliclazide: 11

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
CYP2C9, KCNJ11 and ABCC8 polymorphisms and the response to sulphonylurea treatment in type 2 diabetes patients. European journal of clinical pharmacology. 2014. Klen Jasna, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
KCNJ11 gene E23K variant and therapeutic response to sulfonylureas. European journal of internal medicine. 2012. Javorsky Martin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic risk factors for type 2 diabetes mellitus and response to sulfonylurea treatment. Pharmacogenetics and genomics. 2011. Swen Jesse J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Effect of CYP2C9 polymorphisms on prescribed dose and time-to-stable dose of sulfonylureas in primary care patients with Type 2 diabetes mellitus. Pharmacogenomics. 2010. Swen Jesse J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Loss-of-function CYP2C9 variants improve therapeutic response to sulfonylureas in type 2 diabetes: a Go-DARTS study. Clinical pharmacology and therapeutics. 2010. Zhou K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Presence of CYP2C9*3 allele increases risk for hypoglycemia in Type 2 diabetic patients treated with sulfonylureas. Pharmacogenomics. 2009. Ragia Georgia, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of glucose-lowering drug treatment: a systematic review. Molecular diagnosis & therapy. 2007. Bozkurt Ozlem, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Lymphocyte ecto-5'-nucleotidase in obese type 2 diabetic patients treated with gliclazide. Diabetes & metabolism. 2006. Stefanovic V, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Differential selectivity of insulin secretagogues: mechanisms, clinical implications, and drug interactions. Journal of diabetes and its complications. 2003. Gribble Fiona M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53). Diabetic medicine : a journal of the British Diabetic Association. 2001. Gloyn A L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Sulfonylurea sensitivity of adenosine triphosphate-sensitive potassium channels from beta cells and extrapancreatic tissues. Metabolism: clinical and experimental. 2000. Gribble F M, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01120
ChEBI:
31654
KEGG Drug:
D01599
PubChem Compound:
3475
PubChem Substance:
46505475
Drugs Product Database (DPD):
2248453
ChemSpider:
3356
Therapeutic Targets Database:
DAP000522

Clinical Trials

These are trials that mention gliclazide and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.