Identification

Name
Sitagliptin
Accession Number
DB01261  (DB07214)
Type
Small Molecule
Groups
Approved, Investigational
Description

Sitagliptin is a new oral hypoglycemic (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. This enzyme-inhibiting drug is to be used either alone or in combination with metformin or a thiazolidinedione for control of type 2 diabetes mellitus. The drug works to competitively inhibit a protein/enzyme, dipeptidyl peptidase 4 (DPP-4), that results in an increased amount of active incretins (GLP-1 and GIP), reduced amount of release of glucagon (diminishes its release) and increased release of insulin.

Structure
Thumb
Synonyms
  • (2R)-4-OXO-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine
  • MK-0431
  • Sitagliptan
  • Sitagliptin phosphate
  • Sitagliptina
  • Sitagliptine
  • Sitagliptinum
External IDs
LEZ-763 / LEZ763 / MK-0431
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
JanuviaTablet, film coated50 mg/1OralCardinal Health2006-10-16Not applicableUs55154 504420180907 15195 d2yu5v
JanuviaTablet, film coated25 mgOralMerck Sharp & Dohme Limited2007-03-21Not applicableEu
JanuviaTablet, film coated25 mg/1OralA-S Medication Solutions2006-10-16Not applicableUs
JanuviaTablet, film coated100 mgOralMerck Sharp & Dohme Limited2007-03-21Not applicableEu
JanuviaTablet, film coated100 mgOralMerck Sharp & Dohme Limited2007-03-21Not applicableEu
JanuviaTablet, film coated100 mg/1OralClinical Solutions Wholsesale2006-10-16Not applicableUs58118 027720180907 15195 ngjdr0
JanuviaTablet100 mgOralMerck Ltd.2008-01-02Not applicableCanada
JanuviaTablet, film coated25 mg/1OralMerck Sharp & Dohme Limited2006-10-16Not applicableUs00006 0221 31 nlmimage10 da15ed0f
JanuviaTablet, film coated50 mgOralMerck Sharp & Dohme Limited2007-03-21Not applicableEu
JanuviaTablet, film coated50 mg/1OralCardinal Health2006-10-16Not applicableUs55154 504020180913 8702 1xonqx6
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
JanumetSitagliptin (50 mg) + Metformin Hydrochloride (850 mg)Tablet, film coatedOralMerck Sharp & Dohme Limited2008-07-16Not applicableEu
JanumetSitagliptin (50 mg/1) + Metformin Hydrochloride (500 mg/1)Tablet, film coatedOralMerck Sharp & Dohme Limited2007-03-30Not applicableUs0006 057520180810 16125 1fdkp22
JanumetSitagliptin (50 mg) + Metformin Hydrochloride (850 mg)Tablet, film coatedOralMerck Sharp & Dohme Limited2008-07-16Not applicableEu
JanumetSitagliptin (50 mg/1) + Metformin Hydrochloride (500 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2008-12-172012-06-30Us
JanumetSitagliptin (50 mg) + Metformin Hydrochloride (500 mg)TabletOralMerck Ltd.2009-10-08Not applicableCanada
JanumetSitagliptin (50 mg) + Metformin Hydrochloride (1000 mg)Tablet, film coatedOralMerck Sharp & Dohme Limited2008-07-16Not applicableEu
JanumetSitagliptin (50 mg) + Metformin Hydrochloride (1000 mg)Tablet, film coatedOralMerck Sharp & Dohme Limited2008-07-16Not applicableEu
JanumetSitagliptin (50 mg/1) + Metformin Hydrochloride (500 mg/1)Tablet, film coatedOralMed Pharma Co., Ltd.2011-07-012012-07-18Us
JanumetSitagliptin (50 mg) + Metformin Hydrochloride (850 mg)Tablet, film coatedOralMerck Sharp & Dohme Limited2008-07-16Not applicableEu
JanumetSitagliptin (50 mg/1) + Metformin Hydrochloride (1000 mg/1)Tablet, film coatedOralRemedy Repack2013-04-022015-08-19Us
International/Other Brands
Xelevia
Categories
UNII
QFP0P1DV7Z
CAS number
486460-32-6
Weight
Average: 407.3136
Monoisotopic: 407.118079357
Chemical Formula
C16H15F6N5O
InChI Key
MFFMDFFZMYYVKS-SECBINFHSA-N
InChI
InChI=1S/C16H15F6N5O/c17-10-6-12(19)11(18)4-8(10)3-9(23)5-14(28)26-1-2-27-13(7-26)24-25-15(27)16(20,21)22/h4,6,9H,1-3,5,7,23H2/t9-/m1/s1
IUPAC Name
(3R)-3-amino-1-[3-(trifluoromethyl)-5H,6H,7H,8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one
SMILES
N[C@@H](CC(=O)N1CCN2C(C1)=NN=C2C(F)(F)F)CC1=CC(F)=C(F)C=C1F

Pharmacology

Indication

For use as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. Also for use in patients with type 2 diabetes mellitus to improve glycemic control in combination with metformin or a PPARγ agonist (e.g., thiazolidinediones) when the single agent alone, with diet and exercise, does not provide adequate glycemic control.

Associated Conditions
Pharmacodynamics

Sitagliptin is an orally-active member of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. The benefit of this medicine is expected to be its lower side-effects of hypoglycemia in the control of blood glucose values. The drug works to diminish the effects of a protein/enzyme (by the inhibition of this protein/enzyme) on the pancreas at the level of release of glucagon (diminishes its release) and at the level of insulin (increases its synthesis and release) until blood glucose levels are restored toward normal, in which case the protein/enzyme-enzyme inhibitor becomes less effective and the amounts of insulin released diminishes thus diminishing the "overshoot" of hypoglycemia seen in other oral hypoglycemic agents.

Mechanism of action

Sitagliptin is a highly selective DPP-4 inhibitor, which is believed to exert its actions in patients with type 2 diabetes by slowing the inactivation of incretin hormones, thereby increasing the concentration and prolonging the action of these hormones. Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released by the intestine throughout the day, and levels are increased in response to a meal. These hormones are rapidly inactivated by the enzyme, DPP-4. The incretins are part of an endogenous system involved in the physiologic regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP increase insulin synthesis and release from pancreatic beta cells by intracellular signaling pathways involving cyclic AMP. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, leading to reduced hepatic glucose production. By increasing and prolonging active incretin levels, sitagliptin increases insulin release and decreases glucagon levels in the circulation in a glucose-dependent manner. These changes lead to a decrease in hemoglobin A1c (HbA1c)levels, as well as a lower fasting and postprandial glucose concentration. Sitagliptin demonstrates selectivity for DPP-4 and does not inhibit DPP-8 or DPP-9 activity in vitro at concentrations approximating those from therapeutic doses.

TargetActionsOrganism
ADipeptidyl peptidase 4
inhibitor
Human
Absorption

Rapidly absorbed following oral administration, with an absolute bioavailability of 87%.

Volume of distribution
  • 198 L [healthy subjects]
Protein binding

The fraction of sitagliptin reversibly bound to plasma proteins is low (38%).

Metabolism

Sitagliptin does not undergo extensive metabolism. In vitro studies indicate that the primary enzyme responsible for the limited metabolism of sitagliptin was CYP3A4 (oxidation), with contribution from CYP2C8.

Route of elimination

Approximately 79% of sitagliptin is excreted unchanged in the urine with metabolism being a minor pathway of elimination. Following administration of an oral [14C]sitagliptin dose to healthy subjects, approximately 100% of the administered radioactivity was eliminated in feces (13%) or urine (87%) within one week of dosing. Elimination of sitagliptin occurs primarily via renal excretion and involves active tubular secretion.

Half life

12.4 hours

Clearance
  • renal cl=350 mL/min [Healthy subjects receiving 100 mg oral dose]
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Sitagliptin can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
AbemaciclibThe serum concentration of Sitagliptin can be increased when it is combined with Abemaciclib.
AcetaminophenThe serum concentration of Sitagliptin can be increased when it is combined with Acetaminophen.
AcetohexamideSitagliptin may increase the hypoglycemic activities of Acetohexamide.
Acetyl sulfisoxazoleThe therapeutic efficacy of Sitagliptin can be increased when used in combination with Acetyl sulfisoxazole.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Sitagliptin.
Adefovir DipivoxilAdefovir Dipivoxil may decrease the excretion rate of Sitagliptin which could result in a higher serum level.
AfatinibThe serum concentration of Sitagliptin can be increased when it is combined with Afatinib.
AlaproclateAlaproclate may increase the hypoglycemic activities of Sitagliptin.
AlbendazoleThe serum concentration of Sitagliptin can be increased when it is combined with Albendazole.
Food Interactions
  • Can be administered without regard to food

References

Synthesis Reference

Nurit Perlman, Marina Etinger, Valerie Niddam-Hildesheim, Mili Abramov, "Preparation of sitagliptin intermediate." U.S. Patent US20090192326, issued July 30, 2009.

US20090192326
General References
  1. Herman GA, Stevens C, Van Dyck K, Bergman A, Yi B, De Smet M, Snyder K, Hilliard D, Tanen M, Tanaka W, Wang AQ, Zeng W, Musson D, Winchell G, Davies MJ, Ramael S, Gottesdiener KM, Wagner JA: Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther. 2005 Dec;78(6):675-88. [PubMed:16338283]
  2. Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan AG, Lasseter K, Dilzer S, Blum R, Wagner JA: Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol. 2006 Aug;46(8):876-86. [PubMed:16855072]
  3. Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP: Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin. 2008 Feb;24(2):489-96. doi: 10.1185/030079908X261069 . [PubMed:18182122]
  4. Pratley RE, Salsali A: Inhibition of DPP-4: a new therapeutic approach for the treatment of type 2 diabetes. Curr Med Res Opin. 2007 Apr;23(4):919-31. [PubMed:17407649]
  5. Bergman A, Ebel D, Liu F, Stone J, Wang A, Zeng W, Chen L, Dilzer S, Lasseter K, Herman G, Wagner J, Krishna R: Absolute bioavailability of sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, in healthy volunteers. Biopharm Drug Dispos. 2007 Sep;28(6):315-22. [PubMed:17575559]
  6. Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch C: Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes. Vasc Health Risk Manag. 2008;4(4):753-68. [PubMed:19065993]
External Links
Human Metabolome Database
HMDB0015390
PubChem Compound
4369359
PubChem Substance
46505822
ChemSpider
3571948
BindingDB
11162
ChEBI
40237
ChEMBL
CHEMBL1422
Therapeutic Targets Database
DAP000639
PharmGKB
PA164748978
HET
715
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Sitagliptin
ATC Codes
A10BH51 — Sitagliptin and simvastatinA10BD12 — Pioglitazone and sitagliptinA10BH01 — SitagliptinA10BD07 — Metformin and sitagliptin
AHFS Codes
  • 68:20.05 — Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
PDB Entries
1x70 / 4ffw

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceHealthy Volunteers1
0CompletedTreatmentCongestive Heart Failure (CHF)1
0WithdrawnTreatmentType 2 Diabetes Mellitus1
1CompletedNot AvailableBMI >30 kg/m21
1CompletedNot AvailableDiabetes Mellitus (DM)1
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of ASP19411
1CompletedNot AvailableType 2 Diabetes Mellitus1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic ScienceType 2 Diabetes Mellitus1
1CompletedDiagnosticCystic Fibrosis (CF)1
1CompletedDiagnosticType 2 Diabetes Mellitus2
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentDiabetes Mellitus (DM) / Gastroparesis1
1CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
1CompletedTreatmentDiabetes, Diabetes Mellitus Type 1 / Type 2 Diabetes Mellitus1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentLiver Insufficiency1
1CompletedTreatmentType 2 Diabetes Mellitus23
1CompletedTreatmentType2 Diabetes Mellitus1
1RecruitingTreatmentHepato Carcinoma1
1RecruitingTreatmentType 2 Diabetes Mellitus1
1TerminatedTreatmentHepatitis C Viral Infection1
1Unknown StatusTreatmentType 2 Diabetes Mellitus1
1, 2CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
1, 2CompletedTreatmentType 2 Diabetes Mellitus1
2CompletedOtherType 2 Diabetes Mellitus1
2CompletedTreatmentAcute Lymphoblastic Leukaemias (ALL) / Leukemia Acute Myeloid Leukemia (AML) / Leukemia, Myelogenous, Chronic / Myelodysplasia / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentAcute Lymphocytic Leukemia (ALL) / Hematopoetic Myelodysplasia / Leukemia Acute Myeloid Leukemia (AML) / Leukemia, Myelogenous, Chronic / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentDiabetes Mellitus (DM)2
2CompletedTreatmentDiabetes Mellitus (DM) / Gastroparesis1
2CompletedTreatmentDiabetes Mellitus, Non Insulin Dependent / Type 2 Diabetes Mellitus1
2CompletedTreatmentDiabetes Mellitus, Non-Insulin-Dependent1
2CompletedTreatmentDiabetes, Diabetes Mellitus Type 12
2CompletedTreatmentGlucose tolerance impaired1
2CompletedTreatmentInfection, Human Immunodeficiency Virus I1
2CompletedTreatmentNon- Alcoholic Fatty Liver Disease / Non-Alcoholic Fatty Liver Disease (NAFLD)1
2CompletedTreatmentPsoriasis1
2CompletedTreatmentPsoriasis / Type 2 Diabetes Mellitus1
2CompletedTreatmentType 2 Diabetes Mellitus23
2Enrolling by InvitationTreatmentPharmacological Action (PA)1
2RecruitingPreventionPosttransplant Diabetes Mellitus1
2RecruitingTreatmentAtherosclerosis / Inflammatory Reaction1
2RecruitingTreatmentGraft Versus Host Disease (GVHD) / Hematopoietic Stem Cell Transplantation (HSCT)1
2RecruitingTreatmentPre-Diabetic1
2TerminatedBasic ScienceType 2 Diabetes Mellitus1
2TerminatedTreatmentCystic Fibrosis (CF)1
2TerminatedTreatmentDiabetes, Autoimmune / Diabetes, Diabetes Mellitus Type 11
2Unknown StatusHealth Services ResearchGlucose Homeostasis1
2Unknown StatusTreatmentDiabetes, Diabetes Mellitus Type 11
2Unknown StatusTreatmentImpaired Glucose Tolerance (IGT)1
2WithdrawnTreatmentType 2 Diabetes Mellitus1
2, 3CompletedNot AvailableDiabetes Mellitus (DM) / Insulin Resistance1
2, 3CompletedBasic ScienceHyperlipidemias1
2, 3CompletedTreatmentDiabetes Mellitus (DM)1
2, 3CompletedTreatmentType 2 Diabetes Mellitus2
2, 3Not Yet RecruitingTreatmentDiabetes Mellitus (DM) / Gastroduodenal Ulcers / Iron Metabolism Disorders / Optic Atrophy / Platelets Dysfunction / Sensorineural Hearing Loss1
2, 3Unknown StatusTreatmentAcute Myocardial Infarction (AMI)1
3Active Not RecruitingTreatmentComparative Effectiveness of Glycemia-lowering Medications / Type 2 Diabetes Mellitus1
3Active Not RecruitingTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus3
3Active Not RecruitingTreatmentType 2 Diabetes Mellitus2
3CompletedBasic ScienceType 2 Diabetes Mellitus1
3CompletedTreatmentCardiovascular Disease (CVD) / Inflammatory Reaction / Macrophage Infiltration1
3CompletedTreatmentCardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
3CompletedTreatmentDiabetes Mellitus (DM) / Postprandial Lipaemia1
3CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus6
3CompletedTreatmentDiabetes Mellitus, Non-Insulin-Dependent3
3CompletedTreatmentDiabetes Mellitus, Non-Insulin-Dependent / Type 2 Diabetes Mellitus, Non Insulin Dependent1
3CompletedTreatmentEnd-Stage Kidney Disease / Type 2 Diabetes Mellitus1
3CompletedTreatmentHyperlipidemias / Type 2 Diabetes Mellitus1
3CompletedTreatmentImpaired Renal Function / Type 2 Diabetes Mellitus1
3CompletedTreatmentRenal Insufficiency,Chronic / Type 2 Diabetes Mellitus2
3CompletedTreatmentType 2 Diabetes Mellitus76
3Not Yet RecruitingTreatmentType 2 Diabetes Mellitus1
3RecruitingPreventionHealthy Volunteers1
3RecruitingTreatmentType 2 Diabetes Mellitus2
3TerminatedPreventionCystic Fibrosis (CF) / Pre-Diabetic1
3TerminatedTreatmentGlycemic Control1
3TerminatedTreatmentImpaired Renal Function / Type 2 Diabetes Mellitus1
3TerminatedTreatmentIslet Transplantation1
3TerminatedTreatmentType 2 Diabetes Mellitus5
3Unknown StatusTreatmentType 2 Diabetes Mellitus1
3WithdrawnPreventionType 2 Diabetes Mellitus1
3WithdrawnTreatmentDiabetic Foot1
3WithdrawnTreatmentType 2 Diabetes Mellitus2
4Active Not RecruitingBasic ScienceHealthy Volunteers1
4Active Not RecruitingOtherPolycystic Ovaries Syndrome1
4Active Not RecruitingTreatmentCholesterol, LDL / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / Dipeptidyl-Peptidase 4 Inhibitors / Glycosylated Hemoglobin1
4CompletedNot AvailableHealthy Volunteers1
4CompletedBasic ScienceAtherosclerosis / Diabetes Mellitus (DM)1
4CompletedBasic ScienceHealthy Volunteers / Type 2 Diabetes Mellitus1
4CompletedBasic ScienceHigh Blood Pressure (Hypertension) / Metabolic Syndromes1
4CompletedBasic ScienceType 2 Diabetes Mellitus4
4CompletedOtherBMI >30 kg/m21
4CompletedPreventionCoronary Artery Disease1
4CompletedPreventionHyperglycemias1
4CompletedPreventionPolycystic Ovarian Syndrome1
4CompletedSupportive CareAcromegaly / Cushing's Disease1
4CompletedTreatmentAtherosclerosis / Type 2 Diabetes Mellitus1
4CompletedTreatmentBMI >30 kg/m2 / General Surgery / Hypoglycemia1
4CompletedTreatmentBody Weights / Polycystic Ovaries Syndrome1
4CompletedTreatmentCoronary Artery Disease / Newly Diagnosed Type 2 Diabetes1
4CompletedTreatmentDIABETES Mellitus Type 2 Not Well Controlled1
4CompletedTreatmentDiabetes Ketoacidosis / Hyperglycemias / Ketosis Prone Diabetes1
4CompletedTreatmentDiabetes Mellitus (DM)5
4CompletedTreatmentDiabetes Mellitus (DM) / Impaired Glucose Tolerance (IGT) / Myocardial Infarction / Unstable Angina Pectoris1
4CompletedTreatmentDiabetes Mellitus (DM) / Pancreatitis1
4CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus3
4CompletedTreatmentDiabetes, Diabetes Mellitus Type 13
4CompletedTreatmentDisorder of Glucose Regulation1
4CompletedTreatmentGlucose tolerance impaired1
4CompletedTreatmentHospitalization / Hyperglycemias / Type 2 Diabetes Mellitus1
4CompletedTreatmentNeoplasms, Adipose Tissue1
4CompletedTreatmentNon-Alcoholic Fatty Liver Disease (NAFLD)1
4CompletedTreatmentPre-Diabetic1
4CompletedTreatmentReactive Hypoglycemia1
4CompletedTreatmentType 2 Diabetes Mellitus25
4Enrolling by InvitationTreatmentType 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentAtherosclerosis Type 2 Diabetes Mellitus Dipeptidyl Peptidase-4 Inhibitor GLP-11
4RecruitingBasic ScienceBMI >30 kg/m2 / Pre-Diabetic1
4RecruitingHealth Services ResearchType 2 Diabetes Mellitus1
4RecruitingPreventionHyperglycemias1
4RecruitingTreatmentAcute Coronary Syndromes (ACS) / Type 2 Diabetes Mellitus1
4RecruitingTreatmentCoronary Heart Disease (CHD) / Diabetes Mellitus (DM)1
4RecruitingTreatmentDiabetes Mellitus (DM)1
4RecruitingTreatmentHeart Failure, Systolic / Type 2 Diabetes Mellitus1
4RecruitingTreatmentHeart Failure, Unspecified / Type 2 Diabetes Mellitus1
4RecruitingTreatmentShort Bowel Syndrome (SBS)1
4RecruitingTreatmentType 2 Diabetes Mellitus9
4RecruitingTreatmentType II Diabetes in Subjects BMI 27 to 32 / Type II Diabetes in the Not so Obese1
4TerminatedTreatmentDiabetes Mellitus (DM) / End Stage Renal Disease (ESRD) / Transplant, Kidney / Type 2 Diabetes Mellitus1
4TerminatedTreatmentDiabetes Mellitus (DM) / Hypoglycemia1
4TerminatedTreatmentHyperglycemias / Type 2 Diabetes Mellitus1
4TerminatedTreatmentMicroalbuminuria / Microalbuminuria in Type Two Diabetes / Type 2 Diabetes Mellitus1
4TerminatedTreatmentType 2 Diabetes Mellitus5
4Unknown StatusNot AvailableType 2 Diabetes Mellitus2
4Unknown StatusBasic ScienceType 2 Diabetes Mellitus1
4Unknown StatusTreatmentChronic Liver Diseases (CLD) / Type 2 Diabetes Mellitus1
4Unknown StatusTreatmentDiabetes, Diabetes Mellitus Type 11
4Unknown StatusTreatmentType 2 Diabetes Mellitus4
4WithdrawnTreatmentNon-Alcoholic Fatty Liver Disease (NAFLD) / Type 2 Diabetes Mellitus1
Not AvailableActive Not RecruitingTreatmentDiabetes Mellitus (DM)1
Not AvailableCompletedNot AvailableDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableDiabetes, Diabetes Mellitus Type 1 / Hypoglycemia1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus9
Not AvailableCompletedBasic ScienceObesity, Severe1
Not AvailableCompletedOtherCardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
Not AvailableCompletedPreventionBMI >30 kg/m2 / Type 2 Diabetes Mellitus1
Not AvailableCompletedPreventionBeta-cell Function / Diabetes Mellitus (DM) / Glucocorticoid-induced Diabetes / Steroid Diabetes1
Not AvailableCompletedSupportive CareDiabetes, Diabetes Mellitus Type 11
Not AvailableCompletedTreatmentBMI >30 kg/m21
Not AvailableCompletedTreatmentDiabetes Mellitus, Non-Insulin-Dependent1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentImpaired Fasting Glucose (IFG) / Impaired Glucose Tolerance (IGT) / Pre-Diabetic1
Not AvailableCompletedTreatmentPre-Diabetic / Type 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentType 2 Diabetes Mellitus6
Not AvailableCompletedTreatmentType 2 Diabetes Mellitus / Type2 Diabetes Mellitus1
Not AvailableNot Yet RecruitingNot AvailableType 2 Diabetes Mellitus3
Not AvailableNot Yet RecruitingTreatmentType 2 Diabetes Mellitus1
Not AvailableRecruitingBasic SciencePhysiology1
Not AvailableRecruitingOtherCystic Fibrosis (CF) / Pancreatic Insufficiency1
Not AvailableRecruitingOtherType 2 Diabetes Mellitus1
Not AvailableRecruitingPreventionIncretinomimetics / Pancreas / Type 2 Diabetes Mellitus1
Not AvailableRecruitingTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
Not AvailableRecruitingTreatmentPre-Diabetic / Type 2 Diabetes Mellitus1
Not AvailableRecruitingTreatmentType 2 Diabetes Mellitus1
Not AvailableTerminatedNot AvailableType 2 Diabetes Mellitus1
Not AvailableTerminatedPreventionPrediabetic State1
Not AvailableTerminatedTreatmentNonalcoholic Steatohepatitis / Type 2 Diabetes Mellitus1
Not AvailableUnknown StatusNot AvailableArterial Stiffness / Diabetes Mellitus (DM)1
Not AvailableUnknown StatusTreatmentDiabetes Type I1
Not AvailableUnknown StatusTreatmentTransplant, Kidney / Type 2 Diabetes Mellitus1
Not AvailableUnknown StatusTreatmentType 2 Diabetes Mellitus3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Lake Erie Medical and Surgical Supply
  • Merck & Co.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
Dosage forms
FormRouteStrength
TabletOral
Tablet, extended releaseOral
Tablet, film coated, extended releaseOral
TabletOral100 mg
TabletOral25 mg
TabletOral50 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral25 mg
Tablet, film coatedOral50 mg/1
Tablet, film coatedOral50 mg
Tablet, film coatedOral
Prices
Unit descriptionCostUnit
Januvia 90 25 mg tablet Bottle686.36USD bottle
Januvia 30 100 mg tablet Bottle228.81USD bottle
Januvia 50 mg tablet7.48USD tablet
Januvia 100 mg tablet7.33USD tablet
Januvia 25 mg tablet7.33USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
CA2536251No2009-08-042024-08-27Canada
CA2450740No2006-02-142022-07-05Canada
US7326708No2006-04-112026-04-11Us
US6699871No2002-07-262022-07-26Us
US7125873No2002-07-262022-07-26Us
US8414921No2008-07-212028-07-21Us
US6340475No1996-09-192016-09-19Us
US6635280No1996-09-192016-09-19Us
US6303661No1997-04-242017-04-24Us
US6890898No1999-02-022019-02-02Us
US7078381No1999-02-022019-02-02Us
US7459428No1999-02-022019-02-02Us
US8168637No2002-06-262022-06-26Us
US8080580No2010-07-132030-07-13Us
US9439901No2010-10-212030-10-21Us
US9308204No2010-10-212030-10-21Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.034 mg/mLALOGPS
logP1.95ALOGPS
logP1.26ChemAxon
logS-4.1ALOGPS
pKa (Strongest Basic)8.78ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area77.04 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity87.49 m3·mol-1ChemAxon
Polarizability32.66 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9438
Caco-2 permeable-0.6415
P-glycoprotein substrateSubstrate0.6509
P-glycoprotein inhibitor IInhibitor0.7141
P-glycoprotein inhibitor IIInhibitor0.5248
Renal organic cation transporterInhibitor0.592
CYP450 2C9 substrateNon-substrate0.9277
CYP450 2D6 substrateNon-substrate0.7228
CYP450 3A4 substrateSubstrate0.6412
CYP450 1A2 substrateNon-inhibitor0.7178
CYP450 2C9 inhibitorInhibitor0.6111
CYP450 2D6 inhibitorNon-inhibitor0.538
CYP450 2C19 inhibitorInhibitor0.7048
CYP450 3A4 inhibitorInhibitor0.5358
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8336
Ames testNon AMES toxic0.5487
CarcinogenicityNon-carcinogens0.7973
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.8093 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7076
hERG inhibition (predictor II)Inhibitor0.6936
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
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-0000900000-ce9211ae5927c697618c
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-052r-0690500000-c28779e719a0e517d106
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0076-0930000000-1337dd7fb10ab92722b5
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00dl-0900000000-91485eb0052ad2f3637a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0900000000-7d92431093315efaed86
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0390000000-c8853d370b51f01b194b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000900000-2895dd4a879799635ae6
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-007c-0970100000-17431cd80097dff5c35f
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00dl-0910000000-29041ebd42cb7f6026df
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0900000000-dc60c3b1e5f0ba0e5e23
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0umi-0900000000-b1e1f886377c8d9b2a5d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0900000000-d9e2b332d0ff3c6e283b
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-0000900000-3403c0e74f19a7d0832a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-007c-0970000000-6aa1fc14d171d0102a2c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00dl-0910000000-62ba59074d19e0d89306
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00di-0900000000-91600010aa7e80c0e67c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0fmi-0900000000-d38f8b74df088a3b8232
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0900000000-08cf9f4ac284f2cd9057
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-000i-0390000000-b6e5cd73f4ff7abd2747

Taxonomy

Description
This compound belongs to the class of organic compounds known as beta amino acids and derivatives. These are amino acids having a (-NH2) group attached to the beta carbon atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Beta amino acids and derivatives
Alternative Parents
Amphetamines and derivatives / Triazolopyrazines / Aralkylamines / Fluorobenzenes / Pyrazines / Aryl fluorides / Triazoles / Tertiary carboxylic acid amides / Heteroaromatic compounds / Azacyclic compounds
show 7 more
Substituents
Beta amino acid or derivatives / Amphetamine or derivatives / Triazolopyrazine / Fluorobenzene / Halobenzene / Aralkylamine / Aryl fluoride / Aryl halide / Monocyclic benzene moiety / Pyrazine
show 25 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
trifluorobenzene, triazolopyrazine (CHEBI:40237)

Targets

Details
1. Dipeptidyl peptidase 4
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Virus receptor activity
Specific Function
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by bindi...
Gene Name
DPP4
Uniprot ID
P27487
Uniprot Name
Dipeptidyl peptidase 4
Molecular Weight
88277.935 Da
References
  1. Herman GA, Stevens C, Van Dyck K, Bergman A, Yi B, De Smet M, Snyder K, Hilliard D, Tanen M, Tanaka W, Wang AQ, Zeng W, Musson D, Winchell G, Davies MJ, Ramael S, Gottesdiener KM, Wagner JA: Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther. 2005 Dec;78(6):675-88. [PubMed:16338283]
  2. Bergman AJ, Stevens C, Zhou Y, Yi B, Laethem M, De Smet M, Snyder K, Hilliard D, Tanaka W, Zeng W, Tanen M, Wang AQ, Chen L, Winchell G, Davies MJ, Ramael S, Wagner JA, Herman GA: Pharmacokinetic and pharmacodynamic properties of multiple oral doses of sitagliptin, a dipeptidyl peptidase-IV inhibitor: a double-blind, randomized, placebo-controlled study in healthy male volunteers. Clin Ther. 2006 Jan;28(1):55-72. [PubMed:16490580]
  3. Gallwitz B: Therapies for the treatment of type 2 diabetes mellitus based on incretin action. Minerva Endocrinol. 2006 Jun;31(2):133-47. [PubMed:16682937]
  4. Herman GA, Bergman A, Liu F, Stevens C, Wang AQ, Zeng W, Chen L, Snyder K, Hilliard D, Tanen M, Tanaka W, Meehan AG, Lasseter K, Dilzer S, Blum R, Wagner JA: Pharmacokinetics and pharmacodynamic effects of the oral DPP-4 inhibitor sitagliptin in middle-aged obese subjects. J Clin Pharmacol. 2006 Aug;46(8):876-86. [PubMed:16855072]
  5. Miller S, St Onge EL: Sitagliptin: a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Ann Pharmacother. 2006 Jul-Aug;40(7-8):1336-43. [PubMed:16868220]
  6. Karasik A, Aschner P, Katzeff H, Davies MJ, Stein PP: Sitagliptin, a DPP-4 inhibitor for the treatment of patients with type 2 diabetes: a review of recent clinical trials. Curr Med Res Opin. 2008 Feb;24(2):489-96. doi: 10.1185/030079908X261069 . [PubMed:18182122]
  7. Pratley RE, Salsali A: Inhibition of DPP-4: a new therapeutic approach for the treatment of type 2 diabetes. Curr Med Res Opin. 2007 Apr;23(4):919-31. [PubMed:17407649]
  8. Lyseng-Williamson KA: Sitagliptin. Drugs. 2007;67(4):587-97. [PubMed:17352516]
  9. Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab. 2007 Sep;9(5):733-45. Epub 2007 Jun 26. [PubMed:17593236]
  10. Gallwitz B: Sitagliptin: Profile of a novel DPP-4 inhibitor for the treatment of type 2 diabetes. Drugs Today (Barc). 2007 Jan;43(1):13-25. [PubMed:17315049]
  11. Richter B, Bandeira-Echtler E, Bergerhoff K, Lerch C: Emerging role of dipeptidyl peptidase-4 inhibitors in the management of type 2 diabetes. Vasc Health Risk Manag. 2008;4(4):753-68. [PubMed:19065993]
  12. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Scheen AJ: Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58. doi: 10.1111/j.1463-1326.2010.01212.x. [PubMed:20590741]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Scheen AJ: Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58. doi: 10.1111/j.1463-1326.2010.01212.x. [PubMed:20590741]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Scheen AJ: Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58. doi: 10.1111/j.1463-1326.2010.01212.x. [PubMed:20590741]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Curator comments
Substrate profile was demonstrated in vitro using human OAT3 expressed on CHO-K1 cells.
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. VanWert AL, Gionfriddo MR, Sweet DH: Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology. Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693. [PubMed:19953504]

Drug created on May 16, 2007 11:36 / Updated on September 25, 2018 17:45