Chemical: Drug
glipizide

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.


last updated 12/17/2013

1. FDA Label for glipizide and G6PD

Actionable PGx

Summary

The FDA-approved drug label for glipizide (GLUCOTROL) states that caution should be used in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency due to the risk for hemolytic anemia, and that a non-sulfonylurea alternative should be considered in this subset of patients. G6PD deficiency is a condition caused by variants in the G6PD gene which can be determined by enzymatic or genetic tests, however the drug label does not specifically mention testing.

Annotation

Glipizide (GLUCOTROL) is a blood-glucose-lowering drug indicated for use in adults with type 2 diabetes mellitus as an adjunct to diet and exercise.

Excerpt from the glipizide (GLUCOTROL) drug label:

Hemolytic Anemia: Treatment of patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents can lead to hemolytic anemia. Because GLUCOTROL belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD deficiency and a non-sulfonylurea alternative should be considered.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the glipizide drug label.

*Disclaimer: The contents of this page are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Diabetes Mellitus
    • Indications & usage section, Contraindications section, Warnings section, Precautions section
    • source: PHONT
  • G6PD
    • toxicity, Precautions section
    • source: U.S. Food and Drug Administration

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

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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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.

List of all variant annotations for glipizide

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA CYP2C9 *1 N/A N/A N/A
VIP No VIP available VA CYP2C9 *2 N/A N/A N/A
VIP No VIP available VA CYP2C9 *3 N/A N/A N/A
VIP No Clinical Annotations available No Variant Annotations available
rs1057910 NC_000010.10:g.96741053A=, NC_000010.10:g.96741053A>C, NC_000010.11:g.94981296A=, NC_000010.11:g.94981296A>C, NG_008385.1:g.47639A=, NG_008385.1:g.47639A>C, NM_000771.3:c.1075A=, NM_000771.3:c.1075A>C, NP_000762.2:p.Ile359=, NP_000762.2:p.Ile359Leu, XM_005269575.1:c.1075A=, XM_005269575.1:c.1075A>C, XP_005269632.1:p.Ile359=, XP_005269632.1:p.Ile359Leu, rs17847042, rs3198471, rs61212474
A > C
SNP
I359L
VIP No Clinical Annotations available No Variant Annotations available
rs1799853 NC_000010.10:g.96702047C=, NC_000010.10:g.96702047C>T, NC_000010.11:g.94942290C=, NC_000010.11:g.94942290C>T, NG_008385.1:g.8633C=, NG_008385.1:g.8633C>T, NM_000771.3:c.430C=, NM_000771.3:c.430C>T, NP_000762.2:p.Arg144=, NP_000762.2:p.Arg144Cys, XM_005269575.1:c.430C=, XM_005269575.1:c.430C>T, XP_005269632.1:p.Arg144=, XP_005269632.1:p.Arg144Cys, rs17110268, rs28371674, rs33968134, rs60690363
C > T
SNP
R144C
No VIP available No Clinical Annotations available VA
rs5215 NC_000011.10:g.17387083C>T, NC_000011.9:g.17408630C>T, NG_012446.1:g.6577G>A, NM_000525.3:c.1009G>A, NM_001166290.1:c.748G>A, NP_000516.3:p.Val337Ile, NP_001159762.1:p.Val250Ile, XM_005252910.1:c.838G>A, XM_006718226.2:c.748G>A, XP_005252967.1:p.Val280Ile, XP_006718289.1:p.Val250Ile, XR_930867.1:n.1167G>A, rs56731467
C > T
SNP
V337I
No VIP available No Clinical Annotations available VA
rs5219 NC_000011.10:g.17388025T>C, NC_000011.9:g.17409572T>C, NG_012446.1:g.5635A>G, NM_000525.3:c.67A>G, NM_001166290.1:c.-16-179A>G, NP_000516.3:p.Lys23Glu, XM_005252910.1:c.67A>G, XM_006718226.2:c.-16-179A>G, XP_005252967.1:p.Lys23Glu, XR_930867.1:n.225A>G, rs117591309, rs193929332, rs386597997, rs57819118, rs80356607
T > C
SNP
K23E
No VIP available No Clinical Annotations available VA
rs757110 NC_000011.10:g.17396930C>A, NC_000011.9:g.17418477C>A, NG_008867.1:g.84973G>T, NM_000352.4:c.4105G>T, NM_001287174.1:c.4108G>T, NP_000343.2:p.Ala1369Ser, NP_001274103.1:p.Ala1370Ser, XM_005253088.1:c.4108G>T, XM_011520331.1:c.4105G>T, XM_011520332.1:c.4108G>T, XM_011520333.1:c.2605G>T, XP_005253145.1:p.Ala1370Ser, XP_011518633.1:p.Ala1369Ser, XP_011518634.1:p.Ala1370Ser, XP_011518635.1:p.Ala869Ser, XR_930890.1:n.4171G>T, rs11550111, rs12805113, rs17846753, rs1799855, rs386611540, rs61106969
C > A
SNP
A1369S
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
  • Glipizida [INN-Spanish]
  • Glipizidum [INN-Latin]
  • Glydiazinamide
Trade Names
  • Aldiab
  • Digrin
  • Dipazide
  • Glibenese
  • Glibetin
  • Glican
  • Glide
  • Glidiab
  • Glipid
  • Glipizide Extended-Release Tablets
  • Gluco-Rite
  • Glucolip
  • Glucotrol
  • Glucotrol XL
  • Glucozide
  • Glupitel
  • Glupizide
  • Glyde
  • Melizide
  • Metaglip
  • Mindiab
  • Minidab
  • Minidiab
  • Minodiab
  • Napizide
  • Ozidia
  • Sucrazide
Brand Mixture Names

PharmGKB Accession Id

PA449762

Type(s):

Drug

Description

An oral hypoglycemic agent which is rapidly absorbed and completely metabolized.

Source: Drug Bank

Indication

For use as an adjunct to diet for the control of hyperglycemia and its associated symptomatology in patients with non-insulin-dependent diabetes mellitus (NIDDM; type II), formerly known as maturity-onset diabetes, after an adequate trial of dietary therapy has proved unsatisfactory.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.

Source: Drug Bank

Pharmacology

Glipizide, a second-generation sulfonylurea, is used with diet to lower blood glucose in patients with diabetes mellitus type II. The primary mode of action of glipizide in experimental animals appears to be the stimulation of insulin secretion from the beta cells of pancreatic islet tissue and is thus dependent on functioning beta cells in the pancreatic islets. In humans glipizide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. In man, stimulation of insulin secretion by glipizide in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term glipizide administration, but the postprandial insulin response continues to be enhanced after at least 6 months of treatment. Some patients fail to respond initially, or gradually lose their responsiveness to sulfonylurea drugs, including glipizide.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Take 30-60 minutes before breakfast.|Avoid sugar and sugary food.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. The major metabolites of glipizide are products of aromatic hydroxylation and have no hypoglycemic activity. A minor metabolite which accounts for less than 2% of a dose, an acetylaminoethyl benzine derivatives, is reported to have 1/10 to 1/3 as much hypoglycemic activity as the parent compound.

Source: Drug Bank

Protein Binding

98-99%, primarily to albumin.

Source: Drug Bank

Absorption

Gastrointestinal absorption is uniform, rapid, and essentially complete.

Source: Drug Bank

Half-Life

2-5 hours

Source: Drug Bank

Toxicity

The acute oral toxicity was extremely low in all species tested (LD50 greater than 4 g/kg). Overdosage of sulfonylureas including glipizide can produce hypoglycemia.

Source: Drug Bank

Route of Elimination

The primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine.

Source: Drug Bank

Volume of Distribution

  • 11 L

Source: Drug Bank

Chemical Properties

Chemical Formula

C21H27N5O4S

Source: Drug Bank

Isomeric SMILES

Cc1cnc(cn1)C(=O)NCCc2ccc(cc2)S(=O)(=O)NC(=O)NC3CCCCC3

Source: OpenEye

Canonical SMILES

CC1=CN=C(C=N1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1

Source: Drug Bank

Average Molecular Weight

445.535

Source: Drug Bank

Monoisotopic Molecular Weight

445.178375067

Source: Drug Bank

SMILES

CC1=CN=C(C=N1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NC1CCCCC1

Source: Drug Bank

InChI String

InChI=1S/C21H27N5O4S/c1-15-13-24-19(14-23-15)20(27)22-12-11-16-7-9-18(10-8-16)31(29,30)26-21(28)25-17-5-3-2-4-6-17/h7-10,13-14,17H,2-6,11-12H2,1H3,(H,22,27)(H2,25,26,28)

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 ?

Drug Targets

Gene Description
ABCC8 (source: Drug Bank)
KCNJ1 (source: Drug Bank)
PPARG (source: Drug Bank)

Drug Interactions

Interaction Description
acebutolol - glipizide Decreased in symptoms of hypoglycemia and increase in time required for the body to compensate for hypoglycemia (source: Drug Bank)
acebutolol - glipizide Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia. (source: Drug Bank)
aspirin - glipizide The salicylate increases the effect of sulfonylurea (source: Drug Bank)
aspirin - glipizide Acetylsalicylic acid increases the effect of the sulfonylurea, glipizide. (source: Drug Bank)
atenolol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
atenolol - glipizide The beta-blocker, atenolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
bisoprolol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
bisoprolol - glipizide The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
carvedilol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
carvedilol - glipizide The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
chloramphenicol - glipizide The agent increases the effect of sulfonylurea (source: Drug Bank)
chloramphenicol - glipizide The agent increases the effect of sulfonylurea (source: Drug Bank)
clofibrate - glipizide The agent increases the effect of sulfonylurea (source: Drug Bank)
clofibrate - glipizide The agent increases the effect of sulfonylurea (source: Drug Bank)
cyclosporine - glipizide The sulfonylurea increases the effect of cyclosporine (source: Drug Bank)
cyclosporine - glipizide The sulfonylurea increases the effect of cyclosporine (source: Drug Bank)
esmolol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
esmolol - glipizide The beta-blocker, esmolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
glipizide - somatropin recombinant Somatropin may antagonize the hypoglycemic effect of glipizide. Monitor for changes in fasting and postprandial blood sugars. (source: Drug Bank)
isocarboxazid - glipizide The MAO inhibitor increases the effect of hypoglycemic agent (source: Drug Bank)
labetalol - glipizide The beta-blocker, labetalol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
metoprolol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
metoprolol - glipizide The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
nadolol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
nadolol - glipizide The beta-blocker, nadolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
oxprenolol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
oxprenolol - glipizide The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
phenelzine - glipizide The MAO inhibitor increases the effect of the hypoglycemic agent (source: Drug Bank)
phenylbutazone - glipizide Phenylbutazone increases the effect of the hypoglycemic agent (source: Drug Bank)
phenylbutazone - glipizide Phenylbutazone increases the effect of the hypoglycemic agent (source: Drug Bank)
pindolol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
pindolol - glipizide The beta-blocker, pindolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
propranolol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
propranolol - glipizide The beta-blocker, propranolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
repaglinide - glipizide Similar mode of action - questionable association (source: Drug Bank)
rifampin - glipizide Rifampin decreases the effect of sulfonylurea (source: Drug Bank)
rifampin - glipizide Rifampin decreases the effect of sulfonylurea (source: Drug Bank)
timolol - glipizide The beta-blocker decreases the symptoms of hypoglycemia (source: Drug Bank)
timolol - glipizide The beta-blocker, timolol, may decrease symptoms of hypoglycemia. (source: Drug Bank)
tolbutamide - glipizide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Glipizide. Consider alternate therapy or monitor for changes in Glipizide therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed. (source: Drug Bank)
tolbutamide - glipizide Tolbutamide, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Glipizide. Consider alternate therapy or monitor for changes in Glipizide therapeutic and adverse effects if Tolbutamide is initiated, discontinued or dose changed. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to glipizide: 9

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH): Design of a pharmacogenetic Resource for Type 2 Diabetes. PloS one. 2015. Walford Geoffrey A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available 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 No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacoepidemiologic and in Vitro Evaluation of Potential Drug-Drug Interactions of Sulfonylureas with Fibrates and Statins. British journal of clinical pharmacology. 2014. Schelleman H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Cytochrome P450 2C9-CYP2C9. Pharmacogenetics and genomics. 2010. Van Booven Derek, 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
Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Analytical and bioanalytical chemistry. 2008. Zanger Ulrich M, 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
Clinical consequences of cytochrome P450 2C9 polymorphisms. Clinical pharmacology and therapeutics. 2005. Kirchheiner Julia, 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
Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics. 2002. Lee Craig R, 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
Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics. 1999. Kidd R S, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0378-1105-01
DrugBank:
DB01067
KEGG Drug:
D00335
PubChem Compound:
3478
PubChem Substance:
46505865
7847401
BindingDB:
50012956
ChemSpider:
3359
Therapeutic Targets Database:
DAP000920
FDA Drug Label at DailyMed:
3e21bcc7-6f0d-4d63-befd-aa3ac8c63e37

Clinical Trials

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

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.