Identification

Name
Miglitol
Accession Number
DB00491  (APRD01117)
Type
Small Molecule
Groups
Approved
Description

Miglitol is an oral anti-diabetic drug that acts by inhibiting the ability of the patient to breakdown complex carbohydrates into glucose. It is primarily used in diabetes mellitus type 2 for establishing greater glycemic control by preventing the digestion of carbohydrates (such as disaccharides, oligosaccharides, and polysaccharides) into monosaccharides which can be absorbed by the body.

Miglitol inhibits glycoside hydrolase enzymes called alpha-glucosidases. Since miglitol works by preventing digestion of carbohydrates, it lowers the degree of postprandial hyperglycemia. It must be taken at the start of main meals to have maximal effect. Its effect will depend on the amount of non-monosaccharide carbohydrates in a person's diet.

In contrast to acarbose (another alpha-glucosidase inhibitor), miglitol is systemically absorbed; however, it is not metabolized and is excreted by the kidneys.

Structure
Thumb
Synonyms
  • Miglitol
  • Miglitolum
External IDs
Bay m 1099
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
GlysetTablet, film coated100 mg/1OralPharmacia & Upjohn Inc1996-12-18Not applicableUs
GlysetTablet, film coated50 mg/1OralPhysicians Total Care, Inc.1996-12-182010-06-30Us
GlysetTablet, film coated50 mg/1OralPharmacia & Upjohn Inc1996-12-18Not applicableUs
GlysetTablet, film coated25 mg/1OralPharmacia & Upjohn Inc1996-12-18Not applicableUs00009 5012 01 nlmimage10 8f15c7be
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MiglitolTablet, coated25 mg/1OralSun Pharmaceutical Industries Limited2016-01-04Not applicableUs
MiglitolTablet, coated25 mg/1OralOrient Pharma Co., Ltd.2015-07-31Not applicableUs
MiglitolTablet, coated50 mg/1OralSun Pharmaceutical Industries Limited2016-01-04Not applicableUs
MiglitolTablet, coated100 mg/1OralOrient Pharma Co., Ltd.2015-07-31Not applicableUs
MiglitolTablet, coated100 mg/1OralSun Pharmaceutical Industries Limited2016-01-04Not applicableUs
MiglitolTablet, coated50 mg/1OralOrient Pharma Co., Ltd.2015-07-31Not applicableUs
International/Other Brands
Diaban (Chen Ho) / Diamig (Micro DTF) / Diaset (ACI) / Diastabol (Sanofi-Aventis) / Elitox (Ranbaxy) / Euglitol (Abbott) / Glycet (Pfizer) / Glyset / Laiping (Xinchang Pharmaceutical) / Migbose (Standard) / Miglit (Biocon) / Mignar (Glenmark) / Migtor (Torrent) / Misobit (Lupin) / Plumarol (Lacer) / Seibule (Sanwa Kagaku)
Categories
UNII
0V5436JAQW
CAS number
72432-03-2
Weight
Average: 207.2243
Monoisotopic: 207.110672659
Chemical Formula
C8H17NO5
InChI Key
IBAQFPQHRJAVAV-ULAWRXDQSA-N
InChI
InChI=1S/C8H17NO5/c10-2-1-9-3-6(12)8(14)7(13)5(9)4-11/h5-8,10-14H,1-4H2/t5-,6+,7-,8-/m1/s1
IUPAC Name
(2R,3R,4R,5S)-1-(2-hydroxyethyl)-2-(hydroxymethyl)piperidine-3,4,5-triol
SMILES
OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO

Pharmacology

Indication

For use as an adjunct to diet to improve glycemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM) whose hyperglycemia cannot be managed with diet alone.

Associated Conditions
Pharmacodynamics

Miglitol, an oral alpha-glucosidase inhibitor, is a desoxynojirimycin derivative that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. As a consequence of plasma glucose reduction, miglitol reduce levels of glycosylated hemoglobin in patients with Type II (non-insulin-dependent) diabetes mellitus. Systemic nonenzymatic protein glycosylation, as reflected by levels of glycosylated hemoglobin, is a function of average blood glucose concentration over time. Because its mechanism of action is different, the effect of miglitol to enhance glycemic control is additive to that of sulfonylureas when used in combination. In addition, miglitol diminishes the insulinotropic and weight-increasing effects of sulfonylureas. Miglitol has minor inhibitory activity against lactase and consequently, at the recommended doses, would not be expected to induce lactose intolerance.

Mechanism of action

In contrast to sulfonylureas, miglitol does not enhance insulin secretion. The antihyperglycemic action of miglitol results from a reversible inhibition of membrane-bound intestinal a-glucoside hydrolase enzymes. Membrane-bound intestinal a-glucosidases hydrolyze oligosaccharides and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in delayed glucose absorption and lowering of postprandial hyperglycemia.

TargetActionsOrganism
AMaltase-glucoamylase, intestinal
antagonist
inhibitor
Human
ALysosomal alpha-glucosidase
antagonist
Human
ANeutral alpha-glucosidase AB
antagonist
Human
ANeutral alpha-glucosidase C
antagonist
Human
Absorption

Absorption of miglitol is saturable at high doses with 25 mg being completely absorbed while a 100-mg dose is only 50-70% absorbed. No evidence exists to show that systemic absorption of miglitol adds to its therapeutic effect.

Volume of distribution
  • 0.18 L/kg
Protein binding

The protein binding of miglitol is negligible (<4.0%).

Metabolism

Miglitol is not metabolized in man or in any animal species studied.

Route of elimination

Miglitol is not metabolized in man or in any animal species studied. It is eliminated by renal excretion as an unchanged drug.

Half life

The elimination half-life of miglitol from plasma is approximately 2 hours.

Clearance
Not Available
Toxicity

Unlike sulfonylureas or insulin, an overdose will not result in hypoglycemia. An overdose may result in transient increases in flatulence, diarrhea, and abdomi-nal discomfort. Because of the lack of extra-intestinal effects seen with miglitol, no serious systemic reactions are expected in the event of an overdose.

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

Interactions

Drug Interactions
DrugInteraction
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Miglitol is combined with 2,4-thiazolidinedione.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Miglitol can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Miglitol.
AcetazolamideThe therapeutic efficacy of Miglitol can be increased when used in combination with Acetazolamide.
AcetohexamideThe risk or severity of hypoglycemia can be increased when Miglitol is combined with Acetohexamide.
Acetyl sulfisoxazoleThe therapeutic efficacy of Miglitol can be increased when used in combination with Acetyl sulfisoxazole.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Miglitol.
AICA ribonucleotideThe risk or severity of hypoglycemia can be increased when Miglitol is combined with AICA ribonucleotide.
AlaproclateThe risk or severity of hypoglycemia can be increased when Alaproclate is combined with Miglitol.
AlbiglutideThe risk or severity of hypoglycemia can be increased when Miglitol is combined with Albiglutide.
Food Interactions
  • Take with food, at beginning of each meal. Iron needs increased.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014634
KEGG Drug
D00625
KEGG Compound
C07708
PubChem Compound
441314
PubChem Substance
46504492
ChemSpider
390074
BindingDB
50242271
ChEBI
6935
ChEMBL
CHEMBL1561
Therapeutic Targets Database
DAP000712
PharmGKB
PA164776726
HET
MIG
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Miglitol
ATC Codes
A10BF02 — Miglitol
PDB Entries
3l4w / 5nn6 / 6ca1 / 6ca3
MSDS
Download (68.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of ASP19411
3CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
3CompletedTreatmentType 2 Diabetes Mellitus6
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus3

Pharmacoeconomics

Manufacturers
  • Pharmacia and upjohn co
Packagers
  • Bayer Healthcare
  • Kaiser Foundation Hospital
  • Pharmacia Inc.
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg/1
Tablet, coatedOral100 mg/1
Tablet, coatedOral25 mg/1
Tablet, coatedOral50 mg/1
Prices
Unit descriptionCostUnit
Glyset 100 mg tablet1.46USD tablet
Glyset 50 mg tablet1.24USD tablet
Glyset 25 mg tablet1.11USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)114 °CNot Available
water solubilitySolubleNot Available
logP-2.7Not Available
pKa5.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility610.0 mg/mLALOGPS
logP-2.3ALOGPS
logP-3.2ChemAxon
logS0.47ALOGPS
pKa (Strongest Acidic)12.9ChemAxon
pKa (Strongest Basic)7.6ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area104.39 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity48.16 m3·mol-1ChemAxon
Polarizability20.81 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5422
Blood Brain Barrier-0.8379
Caco-2 permeable-0.7375
P-glycoprotein substrateSubstrate0.6354
P-glycoprotein inhibitor INon-inhibitor0.7325
P-glycoprotein inhibitor IINon-inhibitor0.8248
Renal organic cation transporterNon-inhibitor0.6749
CYP450 2C9 substrateNon-substrate0.8563
CYP450 2D6 substrateNon-substrate0.8168
CYP450 3A4 substrateNon-substrate0.6208
CYP450 1A2 substrateNon-inhibitor0.927
CYP450 2C9 inhibitorNon-inhibitor0.9022
CYP450 2D6 inhibitorNon-inhibitor0.9535
CYP450 2C19 inhibitorNon-inhibitor0.9676
CYP450 3A4 inhibitorNon-inhibitor0.9931
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9968
Ames testNon AMES toxic0.79
CarcinogenicityNon-carcinogens0.9702
BiodegradationNot ready biodegradable0.5392
Rat acute toxicity1.7432 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5797
hERG inhibition (predictor II)Non-inhibitor0.8756
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as piperidines. These are compounds containing a piperidine ring, which is a saturated aliphatic six-member ring with one nitrogen atom and five carbon atoms.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Not Available
Direct Parent
Piperidines
Alternative Parents
Trialkylamines / Secondary alcohols / 1,2-aminoalcohols / Polyols / Azacyclic compounds / Primary alcohols / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Piperidine / 1,2-aminoalcohol / Tertiary aliphatic amine / Tertiary amine / Secondary alcohol / Alkanolamine / Polyol / Azacycle / Organic nitrogen compound / Primary alcohol
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
piperidines (CHEBI:6935)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
Inhibitor
General Function
Maltose alpha-glucosidase activity
Specific Function
May serve as an alternate pathway for starch digestion when luminal alpha-amylase activity is reduced because of immaturity or malnutrition. May play a unique role in the digestion of malted dietar...
Gene Name
MGAM
Uniprot ID
O43451
Uniprot Name
Maltase-glucoamylase, intestinal
Molecular Weight
209850.8 Da
References
  1. Mooradian AD, Thurman JE: Drug therapy of postprandial hyperglycaemia. Drugs. 1999 Jan;57(1):19-29. [PubMed:9951949]
  2. Rossi EJ, Sim L, Kuntz DA, Hahn D, Johnston BD, Ghavami A, Szczepina MG, Kumar NS, Sterchi EE, Nichols BL, Pinto BM, Rose DR: Inhibition of recombinant human maltase glucoamylase by salacinol and derivatives. FEBS J. 2006 Jun;273(12):2673-83. [PubMed:16817895]
  3. Fukaya N, Mochizuki K, Tanaka Y, Kumazawa T, Jiuxin Z, Fuchigami M, Goda T: The alpha-glucosidase inhibitor miglitol delays the development of diabetes and dysfunctional insulin secretion in pancreatic beta-cells in OLETF rats. Eur J Pharmacol. 2009 Dec 10;624(1-3):51-7. doi: 10.1016/j.ejphar.2009.09.048. Epub 2009 Oct 7. [PubMed:19818342]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Maltose alpha-glucosidase activity
Specific Function
Essential for the degradation of glygogen to glucose in lysosomes.
Gene Name
GAA
Uniprot ID
P10253
Uniprot Name
Lysosomal alpha-glucosidase
Molecular Weight
105322.935 Da
References
  1. Fukaya N, Mochizuki K, Tanaka Y, Kumazawa T, Jiuxin Z, Fuchigami M, Goda T: The alpha-glucosidase inhibitor miglitol delays the development of diabetes and dysfunctional insulin secretion in pancreatic beta-cells in OLETF rats. Eur J Pharmacol. 2009 Dec 10;624(1-3):51-7. doi: 10.1016/j.ejphar.2009.09.048. Epub 2009 Oct 7. [PubMed:19818342]
  2. Hirata A, Igarashi M, Iwai H, Tominaga M: Effect of miglitol, an alpha-glucosidase inhibitor, on atherogenic outcomes in balloon-injured diabetic rats. Horm Metab Res. 2009 Mar;41(3):213-20. doi: 10.1055/s-0028-1105919. Epub 2008 Dec 15. [PubMed:19085811]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Poly(a) rna binding
Specific Function
Cleaves sequentially the 2 innermost alpha-1,3-linked glucose residues from the Glc(2)Man(9)GlcNAc(2) oligosaccharide precursor of immature glycoproteins.
Gene Name
GANAB
Uniprot ID
Q14697
Uniprot Name
Neutral alpha-glucosidase AB
Molecular Weight
106873.125 Da
References
  1. Fukaya N, Mochizuki K, Tanaka Y, Kumazawa T, Jiuxin Z, Fuchigami M, Goda T: The alpha-glucosidase inhibitor miglitol delays the development of diabetes and dysfunctional insulin secretion in pancreatic beta-cells in OLETF rats. Eur J Pharmacol. 2009 Dec 10;624(1-3):51-7. doi: 10.1016/j.ejphar.2009.09.048. Epub 2009 Oct 7. [PubMed:19818342]
  2. Hirata A, Igarashi M, Iwai H, Tominaga M: Effect of miglitol, an alpha-glucosidase inhibitor, on atherogenic outcomes in balloon-injured diabetic rats. Horm Metab Res. 2009 Mar;41(3):213-20. doi: 10.1055/s-0028-1105919. Epub 2008 Dec 15. [PubMed:19085811]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Maltose alpha-glucosidase activity
Specific Function
Has alpha-glucosidase activity.
Gene Name
GANC
Uniprot ID
Q8TET4
Uniprot Name
Neutral alpha-glucosidase C
Molecular Weight
104333.445 Da
References
  1. Fukaya N, Mochizuki K, Tanaka Y, Kumazawa T, Jiuxin Z, Fuchigami M, Goda T: The alpha-glucosidase inhibitor miglitol delays the development of diabetes and dysfunctional insulin secretion in pancreatic beta-cells in OLETF rats. Eur J Pharmacol. 2009 Dec 10;624(1-3):51-7. doi: 10.1016/j.ejphar.2009.09.048. Epub 2009 Oct 7. [PubMed:19818342]
  2. Hirata A, Igarashi M, Iwai H, Tominaga M: Effect of miglitol, an alpha-glucosidase inhibitor, on atherogenic outcomes in balloon-injured diabetic rats. Horm Metab Res. 2009 Mar;41(3):213-20. doi: 10.1055/s-0028-1105919. Epub 2008 Dec 15. [PubMed:19085811]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Chloride ion binding
Specific Function
Not Available
Gene Name
AMY2A
Uniprot ID
P04746
Uniprot Name
Pancreatic alpha-amylase
Molecular Weight
57706.51 Da

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 12:49