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Identification
NameEmpagliflozin
Accession NumberDB09038
TypeSmall Molecule
GroupsApproved
Description

Empagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, therefore resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia and also assists weight loss and blood pressure reduction.

Structure
Thumb
Synonyms
(1S)-1,5-anhydro-1-(4-chloro-3-{4-[(3S)-tetrahydrofuran-3-yloxy]benzyl}phenyl)-D-glucitol
1-chloro-4-(glucopyranos-1-yl)-2-(4-(tetrahydrofuran-3-yloxy)benzyl)benzene
External Identifiers
  • BI 10773
  • BI-10773
  • BI10773
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Jardiancetablet, film coated10 mg/1oralBoehringer Ingelheim Pharmaceuticals, Inc.2014-08-01Not applicableUs
Jardiancetablet25 mgoralBoehringer Ingelheim (Canada) Ltd Ltee2015-08-11Not applicableCanada
Jardiancetablet10 mgoralBoehringer Ingelheim (Canada) Ltd Ltee2015-08-11Not applicableCanada
Jardiancetablet, film coated25 mg/1oralBoehringer Ingelheim Pharmaceuticals, Inc.2014-08-01Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
GlyxambiBoehringer Ingelheim Pharmaceuticals, Inc.
SynjardyBoehringer Ingelheim Pharmaceuticals, Inc.
SaltsNot Available
Categories
UNIIHDC1R2M35U
CAS number864070-44-0
WeightAverage: 450.91
Monoisotopic: 450.1445309
Chemical FormulaC23H27ClO7
InChI KeyOBWASQILIWPZMG-QZMOQZSNSA-N
InChI
InChI=1S/C23H27ClO7/c24-18-6-3-14(23-22(28)21(27)20(26)19(11-25)31-23)10-15(18)9-13-1-4-16(5-2-13)30-17-7-8-29-12-17/h1-6,10,17,19-23,25-28H,7-9,11-12H2/t17-,19+,20+,21-,22+,23-/m0/s1
IUPAC Name
(2S,3R,4R,5S,6R)-2-[4-chloro-3-({4-[(3S)-oxolan-3-yloxy]phenyl}methyl)phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol
SMILES
[H][C@@]1(CCOC1)OC1=CC=C(CC2=C(Cl)C=CC(=C2)[C@]2([H])O[C@]([H])(CO)[C@@]([H])(O)[C@]([H])(O)[C@@]2([H])O)C=C1
Taxonomy
ClassificationNot classified
Pharmacology
IndicationEmpagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes.
PharmacodynamicsNot Available
Mechanism of actionEmpagliflozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia, assists weight loss, and reduces blood pressure.
Related Articles
AbsorptionFollowing oral administration, peak plasma concentrations were reached at 1.5 hours post-dose and then declined in a biphasic manner with a rapid distribution phase and a relatively slow terminal phase. Administration following a high-fat and high-calorie meal results in a slightly lower exposure with AUC decreasing by approximately 16% and Cmax decreasing by approximately 37% compared to fasted condition.
Volume of distribution

73.8 L

Protein bindingPlasma protein binding was found to be 86.2%
Metabolism

In vitro studies suggest that empaglifozin is primarily metabolized by glucuronidation by 5'-diphospho-glucuronosyltransferases UG2B7, UGT1A3, UGT1A8, and UGT1A9. The most abundant metabolites are three glucuronide metabolites: 2-O-, 3-O-, and 6-O-glucuronide. Empagliflozin does not inhibit, inactivate, or induce CYP450 isoforms. It is a substrate for p-glycoprotein (p-gp), however in vitro studies suggest that it is unlikely to cause interactions with drugs that are p-gp substrates.

SubstrateEnzymesProduct
Empagliflozin
empagliflozin 3-O-glucuronideDetails
Route of eliminationAfter oral administration, empaglifozin was 41.2% eliminated in feces and 54.4% eliminated in urine.
Half lifeTerminal elimination half life was found to be 12.4 h based on population pharmacokinetic analysis.
Clearance

Apparent oral clearance was found to be 10.6 L/h based on population pharmacokinetic analysis.

ToxicityThe most commonly reported adverse effects for empaglifozin were urinary tract infections, female genital mycotic infections, and dyslipidemia. Because empagliflozin causes osmotic diuresis adverse reactions related to volume depletion were also reported (decreased systolic blood pressure, dehydration, hypotension, orthostatic hypotension, hypovolemia, and syncope). Impaired renal function and hypoglycemia were also reported.
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Tablet, film coatedoral
Tabletoral10 mg
Tabletoral25 mg
Tablet, film coatedoral10 mg/1
Tablet, film coatedoral25 mg/1
Tabletoral
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US6303661 No1997-04-242017-04-24Us
US6890898 No1999-02-022019-02-02Us
US7078381 No1999-02-022019-02-02Us
US7407955 No2003-08-122023-08-12Us
US7459428 No1999-02-022019-02-02Us
US7579449 No2005-11-052025-11-05Us
US7713938 No2007-04-152027-04-15Us
US8119648 No2003-08-122023-08-12Us
US8178541 No2003-08-122023-08-12Us
US8551957 No2009-10-192029-10-19Us
US8673927 No2007-05-042027-05-04Us
US8846695 No2010-06-042030-06-04Us
US8883805 No2005-11-262025-11-26Us
US9173859 No2007-05-042027-05-04Us
USUS7579449 No2005-03-152025-03-15Us
USUS7713938 No2006-04-192026-04-19Us
USWO 201416191 No2014-04-032034-04-03Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.111 mg/mLALOGPS
logP1.79ALOGPS
logP1.66ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)12.57ChemAxon
pKa (Strongest Basic)-3ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area108.61 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity113.79 m3·mol-1ChemAxon
Polarizability45.24 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference
  1. Wang XJ, Zhang L, Byrne D, Nummy L, Weber D, Krishnamurthy D, Yee N, Senanayake CH: Efficient synthesis of Empagliflozin, an inhibitor of SGLT-2, utilizing an AlCl3-promoted silane reduction of a beta-glycopyranoside. Org Lett. 2014 Aug 15;16(16):4090-3. doi: 10.1021/ol501755h. Epub 2014 Jul 25. Pubmed
General References
  1. Scheen AJ: Pharmacokinetics, Pharmacodynamics and Clinical Use of SGLT2 Inhibitors in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease. Clin Pharmacokinet. 2015 Jul;54(7):691-708. doi: 10.1007/s40262-015-0264-4. [PubMed:25805666 ]
  2. Gangadharan Komala M, Mather A: Empagliflozin for the treatment of Type 2 diabetes. Expert Rev Clin Pharmacol. 2014 May;7(3):271-9. doi: 10.1586/17512433.2014.908703. Epub 2014 Apr 9. [PubMed:24716752 ]
  3. Lamos EM, Younk LM, Davis SN: Empagliflozin, a sodium glucose co-transporter 2 inhibitor, in the treatment of type 1 diabetes. Expert Opin Investig Drugs. 2014 Jun;23(6):875-82. doi: 10.1517/13543784.2014.909407. Epub 2014 Apr 19. [PubMed:24746173 ]
  4. Liakos A, Karagiannis T, Athanasiadou E, Sarigianni M, Mainou M, Papatheodorou K, Bekiari E, Tsapas A: Efficacy and safety of empagliflozin for type 2 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab. 2014 Oct;16(10):984-93. doi: 10.1111/dom.12307. Epub 2014 May 28. [PubMed:24766495 ]
  5. Haring HU, Merker L, Seewaldt-Becker E, Weimer M, Meinicke T, Broedl UC, Woerle HJ: Empagliflozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care. 2014 Jun;37(6):1650-9. doi: 10.2337/dc13-2105. Epub 2014 Apr 10. [PubMed:24722494 ]
  6. Neumiller JJ: Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. Drugs Context. 2014 Jun 11;3:212262. doi: 10.7573/dic.212262. eCollection 2014. [PubMed:24991224 ]
  7. Bogdanffy MS, Stachlewitz RF, van Tongeren S, Knight B, Sharp DE, Ku W, Hart SE, Blanchard K: Nonclinical safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin. Int J Toxicol. 2014 Nov-Dec;33(6):436-49. doi: 10.1177/1091581814551648. Epub 2014 Sep 26. [PubMed:25260362 ]
  8. Authors unspecified: Empagliflozin (Jardiance) for diabetes. Med Lett Drugs Ther. 2014 Oct 13;56(1453):99-100. [PubMed:25296258 ]
  9. Jahagirdar V, Barnett AH: Empagliflozin for the treatment of type 2 diabetes. Expert Opin Pharmacother. 2014 Nov;15(16):2429-41. doi: 10.1517/14656566.2014.966078. [PubMed:25301180 ]
External Links
ATC CodesA10BD19A10BD20A10BX12
AHFS Codes
  • 68:20.18
PDB EntriesNot Available
FDA labelDownload (604 KB)
MSDSDownload (99 KB)
Interactions
Drug Interactions
Drug
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Empagliflozin.
AldesleukinThe risk or severity of adverse effects can be increased when Aldesleukin is combined with Empagliflozin.
ButabarbitalButabarbital may increase the hypotensive activities of Empagliflozin.
ButethalButethal may increase the hypotensive activities of Empagliflozin.
ChlorpropamideEmpagliflozin may increase the hypoglycemic activities of Chlorpropamide.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Empagliflozin.
DuloxetineEmpagliflozin may increase the orthostatic hypotensive activities of Duloxetine.
HeptabarbitalHeptabarbital may increase the hypotensive activities of Empagliflozin.
HexobarbitalHexobarbital may increase the hypotensive activities of Empagliflozin.
Insulin HumanEmpagliflozin may increase the hypoglycemic activities of Insulin Regular.
Insulin LisproEmpagliflozin may increase the hypoglycemic activities of Insulin Lispro.
LeuprolideThe therapeutic efficacy of Empagliflozin can be decreased when used in combination with Leuprolide.
LevodopaEmpagliflozin may increase the orthostatic hypotensive activities of Levodopa.
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Empagliflozin.
MethohexitalMethohexital may increase the hypotensive activities of Empagliflozin.
NicorandilNicorandil may increase the hypotensive activities of Empagliflozin.
OxandroloneOxandrolone may increase the hypoglycemic activities of Empagliflozin.
ParoxetineParoxetine may increase the hypoglycemic activities of Empagliflozin.
PegvisomantPegvisomant may increase the hypoglycemic activities of Empagliflozin.
PentobarbitalPentobarbital may increase the hypotensive activities of Empagliflozin.
PhenelzinePhenelzine may increase the hypoglycemic activities of Empagliflozin.
PrimidonePrimidone may increase the hypotensive activities of Empagliflozin.
RisperidoneEmpagliflozin may increase the hypotensive activities of Risperidone.
SecobarbitalSecobarbital may increase the hypotensive activities of Empagliflozin.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Empagliflozin.
TeriflunomideThe serum concentration of Empagliflozin can be increased when it is combined with Teriflunomide.
TestosteroneTestosterone may increase the hypoglycemic activities of Empagliflozin.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Empagliflozin.
TrichlormethiazideThe therapeutic efficacy of Empagliflozin can be decreased when used in combination with Trichlormethiazide.
ValsartanThe risk or severity of adverse effects can be increased when Valsartan is combined with Empagliflozin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonistinhibitor
General Function:
Low-affinity glucose:sodium symporter activity
Specific Function:
Sodium-dependent glucose transporter. Has a Na(+) to glucose coupling ratio of 1:1.Efficient substrate transport in mammalian kidney is provided by the concerted action of a low affinity high capacity and a high affinity low capacity Na(+)/glucose cotransporter arranged in series along kidney proximal tubules.
Gene Name:
SLC5A2
Uniprot ID:
P31639
Molecular Weight:
72895.995 Da
References
  1. Vivian EM: Sodium-glucose co-transporter 2 (SGLT2) inhibitors: a growing class of antidiabetic agents. Drugs Context. 2014 Dec 19;3:212264. doi: 10.7573/dic.212264. eCollection 2014. [PubMed:25598831 ]
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Drug created on March 31, 2015 20:20 / Updated on June 30, 2016 01:52