- Overview
- Properties
- Genetics
- Related Genes
- Pathways
- Related Drugs
- Related Diseases
- Datasets
- Downloads/LinkOuts
Overview
| Generic Names: | Glimepirid; Glimepirida; Glimepiridum; Glimepride |
|---|---|
| IUPAC Name: | 3-ethyl-4-methyl-N-[2-[4-[(4-methylcyclohexyl)carbamoylsulfamoyl]phenyl]ethyl]-2-oxo-5H-pyrrole-1-carboxamide |
| 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.
Indication
For concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.
ATC Therapeutic Category
- A10BB:Sulfonamides, urea derivatives
Pharmacology and Interactions
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.
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.
Food Interactions
Avoid alcohol. Even though food reduces product absorption, the manufacturer recommends taking the product with the first meal of the day.
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.
Protein Binding
Over 99.5% bound to plasma protein.
Absorption
Completely (100%) absorbed following oral administration.
Half Life
Approximately 5 hours following single dose.
Toxicity
Severe hypoglycemic reactions with coma, seizure, or other neurological impairment.
Chemical Properties
Chemical Formula:
C24H34N4O5S
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
(Format: OpenEye Isomeric)
Molecular Weight ( average / monoisotopic )
490.616 / 490.225
Curated Annotations (
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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
-
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
-
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
-
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
Curated Information
The following genes are in curated knowledge about this drug.
| Gene | Relationship | Evidence | |
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ABCC8 |
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AKT1 |
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CACNA1A |
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CACNA1C |
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CACNA1D |
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CYP2C9 |
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GCK |
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HNF1A |
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HNF4A |
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INS |
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INSR |
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IRS1 |
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IRS2 |
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ISL1 |
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KCNJ11 |
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MAFA |
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NEUROD1 |
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NR1I2 |
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PDX1 |
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PIK3C2A |
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PIK3CA |
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PIK3CB |
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PIK3CD |
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PIK3CG |
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PIK3R1 |
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PIK3R2 |
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PIK3R3 |
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PIK3R5 |
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SLC2A2 |
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Non-Curated Information
A list of non-curated publications that mention this drug along with other genes is available.
Metabolizing Enzymes
Drug Targets
PharmGKB Curated Pathways
Non-Curated Information
A list of non-curated publications that mention this drug along with other drugs is available.
Drug Interactions
| cyclosporine | The sulfonylurea increases the effect of cyclosporine |
| gemfibrozil | Gemfibrozil increases the effect and toxicity of rosiglitazone/pioglitazone |
| glucosamine | Possible hyperglycemia |
| ketoconazole | Ketoconazole increases the effect of rosiglitazone |
| pregabalin | Increased risk of edema |
| repaglinide | Similar mode of action - questionable association |
| rifampin | Rifampin reduces levels and efficacy of rosiglitazone, rifampin decreases the effect of sulfonylurea |
Curated Information
The following diseases are in curated knowledge about this drug.
| Disease | Relationship | Evidence | |
|---|---|---|---|
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Diabetes Mellitus |
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Publications, Pathways |
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Diabetes Mellitus, Type 2 |
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Publications, Variants |
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Hypoglycemia |
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Non-Curated Information
A list of non-curated publications that mention this drug along with other diseases is available.
Additional Datasets
These datasets are minimally curated and are sorted alphabetically by title.
LinkOuts
Common Searches
Search PubMed
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Search CTD
Non-Curated Publications
A list of non-curated publications that mention this drug is available.
