PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
glimepiride

2D structure

Overview

Generic Names: Glimepirid; Glimepirida; Glimepiridum; Glimepride
Trade Names: Amarel; Amaryl; Endial; Novo-glimepiride; PMS-glimepiride; Ratio-glimepiride; Sandoz glimepiride
Brand Mixtures: Avandaryl (glimepiride + rosiglitazone maleate)
PharmGKB Accession Id: PA449761

Description

Glimepiride is the first III generation sulphonyl urea it is a very potent sulphonyl urea with long duration of action. (source: Drug Bank)

Indication

For concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus. (source: Drug Bank)

ATC Therapeutic Category

  • A10BB:Sulfonamides, urea derivatives

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

The mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glimepiride likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin. (source: Drug Bank)

Pharmacology

Glimepiride, like glyburide and glipizide, is a "second-generation" sulfonylurea agents. Glimepiride is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Even though food reduces product absorption, the manufacturer recommends taking the product with the first meal of the day. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Following either an intravenous or oral dose, glimepiride is completely metabolized by oxidative biotransformation to a major metabolite, cyclohexyl hydroxymethyl derivative (M1), via the hepatic cytochrome P450 II C9 subsystem. M1 is further metabolized to the carboxyl derivative (M2) by one or several cytosolic enzymes. M1, but not M2, possessed approximately one third of the pharmacologic activity of its parent in an animal model. However, whether the glucose-lowering effect of M1 is clinically significant is not clear. (source: Drug Bank)

Protein Binding

Over 99.5% bound to plasma protein. (source: Drug Bank)

Absorption

Completely (100%) absorbed following oral administration. (source: Drug Bank)

Toxicity

Severe hypoglycemic reactions with coma, seizure, or other neurological impairment. (source: Drug Bank)

Isomeric SMILES Code:

CCC1=C(CN(C1=O)C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)N[C@H]3CC[C@@H](CC3)C)C (source: Drug Bank)

Curated Annotations (Curated Annotation)

  1. rs1799853 at chr10:96692037 in CYP2C9
    In a study of Scottish patients receiving sulfonylureas (n=1073), those with any CYP2C9*2 alleles were less likely to experience treatment failure, and CYP2C9*2 homozygotes had greater reductions in HbA(1c) than CYP2C9*1.
    Variant Name:
    CYP2C9*2, CYP2C9:Arg144Cys
    Related Drugs:
    glibenclamide, gliclazide, glimepiride, glipizide, sulfonamides, urea derivatives
    Related Diseases:
    Diabetes Mellitus
    Evidence:
    PMID:19794412
  2. rs1799853 at chr10:96692037 in CYP2C9
    Risk or phenotype-associated allele: CYP2C9*2, rs1799853 T allele, Cys144. Phenotype: Drug response phenotypes included (1) reaching target HbA(1c), (2) maximum HbA(1c) reduction, and (3) time to monotherapy failure. Patients homozygous for the loss-of-function CYP2C9 alleles (*2/*2, *2/*3, *3/*3) achieved greater treatment target (OR = 3.4, p = 0.0009), 0.5% greater reduction in target HbA1c concentration (p = 0.003), and lower risk of monotherapy failure based an additive genetic model (allelic hazard ratio 0.79, 95% confidence interval 0.63-0.99, p = 0.04), compared to wild-type allele (*1) carriers. Study size: 1,073 patients (578 drug-naive, 495 with prior and continued metformin exposure). Study population/ethnicity: Diabetes patients recruited in Tayside, Scotland for the Diabetes Audit and Research Tayside Study (DARTS), between 1992 and 2007, who were incident sulfonylurea users. Significance metric(s): p = (0.04 - 0.0009) Type of association: GN; PD
    Variant Name:
    CYP2C9*2, c.430C>T, mRNA 455C>T, p.Arg144Cys
    Related Drugs:
    glibenclamide, gliclazide, glimepiride, glipizide, metformin, sulfonamides, urea derivatives
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:19794412
  3. rs1057910 at chr10:96731043 in CYP2C9
    In a study of Scottish patients receiving sulfonylureas (n=1073), those with any CYP2C9*3 alleles were less likely to experience treatment failure, and CYP2C9*3 homozygotes had greater reductions in HbA(1c) than CYP2C9*1.
    Variant Name:
    CYP2C9*3, CYP2C9:Ile359Leu
    Related Drugs:
    glibenclamide, gliclazide, glimepiride, glipizide, sulfonamides, urea derivatives
    Related Diseases:
    Diabetes Mellitus
    Evidence:
    PMID:19794412
  4. rs1057910 at chr10:96731043 in CYP2C9
    Risk or phenotype-associated allele: CYP2C9*3, rs1057910 C allele, Leu359. Phenotype: Drug response phenotypes included (1) reaching target HbA(1c), (2) maximum HbA(1c) reduction, and (3) time to monotherapy failure. Patients homozygous for the loss-of-function CYP2C9 alleles (*2/*2, *2/*3, *3/*3) achieved greater treatment target (OR = 3.4, p = 0.0009), 0.5% greater reduction in target HbA1c concentration (p = 0.003), and lower risk of monotherapy failure based an additive genetic model (allelic hazard ratio 0.79, 95% confidence interval 0.63-0.99, p = 0.04), compared to wild-type allele (*1) carriers. Study size: 1,073 patients (578 drug-naive, 495 with prior and continued metformin exposure). Study population/ethnicity: Diabetes patients recruited in Tayside, Scotland for the Diabetes Audit and Research Tayside Study (DARTS), between 1992 and 2007, who were incident sulfonylurea users. Significance metric(s): p = (0.04 - 0.0009) Type of association: GN; PD
    Variant Name:
    CYP2C9*3, c.1075A>C, mRNA 11A>C, p.Ile359Leu
    Related Drugs:
    glibenclamide, gliclazide, glimepiride, glipizide, metformin, sulfonamides, urea derivatives
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:19794412
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC8
  •   
  • PD
  •   
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
ABCC9
  •   
  • PD
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  • CO
  • PD
  • PK
  • FA
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
NR1I2
  •   
  •   
  •   
  • FA
  •   
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
KCNJ1 Uncurated Annotation (source: Drug Bank)
KCNJ11 Uncurated Annotation (source: Drug Bank)

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
cyclosporine Uncurated Annotation The sulfonylurea increases the effect of cyclosporine (source: Drug Bank)
gemfibrozil Uncurated Annotation Gemfibrozil increases the effect and toxicity of rosiglitazone/pioglitazone (source: Drug Bank)
ketoconazole Uncurated Annotation Ketoconazole increases the effect of rosiglitazone (source: Drug Bank)
repaglinide Uncurated Annotation Similar mode of action - questionable association (source: Drug Bank)
rifampin Uncurated Annotation Rifampin reduces levels and efficacy of rosiglitazone, rifampin decreases the effect of sulfonylurea (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus, Type 2
  • CO
  •   
  • PK
  • FA
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Hypoglycemia
  • CO
  •   
  •   
  •   
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00222
ChEBI ID:
5383
KEGG Compound ID:
C07669
KEGG Drug ID:
D00593
PubChem Compound ID:
3476
PubChem Substance ID:
193913

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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