linagliptin Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
dipeptidyl aminopeptidase-IV inhibitors 4175 668270-12-0

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • linagliptin
  • tradjenta
  • BI 1356
  • BI-1356
Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha cells, resulting in a reduction in hepatic glucose output.
  • Molecular weight: 472.55
  • Formula: C25H28N8O2
  • CLOGP: 1.91
  • LIPINSKI: 0
  • HAC: 10
  • HDO: 1
  • TPSA: 113.48
  • ALOGS: -3.97
  • ROTB: 5

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
5 mg O

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 16 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.90 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 129 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
May 2, 2011 FDA BOEHRINGER INGELHEIM

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Diabetic ketoacidosis 213.93 15.26 100 11567 18110 46656285
Pancreatitis 206.22 15.26 131 11536 43496 46630899
Pemphigoid 177.41 15.26 63 11604 5628 46668767
Hypoglycaemia 175.54 15.26 129 11538 54220 46620175
Blood glucose increased 172.06 15.26 143 11524 71870 46602525
Euglycaemic diabetic ketoacidosis 109.76 15.26 34 11633 1982 46672413
Glycosylated haemoglobin increased 95.52 15.26 49 11618 10827 46663568
Hyperglycaemia 80.23 15.26 68 11599 35003 46639392
Acute kidney injury 69.55 15.26 170 11497 235685 46438710
Renal impairment 67.63 15.26 88 11579 74284 46600111
Hyperlactacidaemia 59.59 15.26 22 11645 2193 46672202
Pancreatic carcinoma 58.89 15.26 30 11637 6527 46667868
Pancreatitis acute 58.47 15.26 49 11618 24823 46649572
Glomerular filtration rate decreased 54.87 15.26 35 11632 11659 46662736
Ketoacidosis 53.57 15.26 24 11643 3931 46670464
Lactic acidosis 52.72 15.26 53 11614 33856 46640539
Diabetic metabolic decompensation 48.14 15.26 16 11651 1169 46673226
Metabolic acidosis 45.13 15.26 52 11615 38728 46635667
Diabetes mellitus inadequate control 44.01 15.26 32 11635 13182 46661213
Hyperkalaemia 42.98 15.26 58 11609 50651 46623744
Blood glucose abnormal 41.69 15.26 24 11643 6648 46667747
Fungal infection 40.23 15.26 43 11624 29477 46644918
Rheumatoid arthritis 36.02 15.26 8 11659 240207 46434188
Dizziness 33.08 15.26 170 11497 340244 46334151
Renal failure 31.39 15.26 80 11587 113514 46560881
Subarachnoid haemorrhage 30.48 15.26 24 11643 11129 46663266
Chronic kidney disease 29.07 15.26 43 11624 40828 46633567
Pain 27.75 15.26 48 11619 476900 46197495
Cardiac failure 27.14 15.26 61 11606 79887 46594508
Shock 26.60 15.26 30 11637 21815 46652580
Blood glucose decreased 26.59 15.26 28 11639 18864 46655531
Hypoglycaemic encephalopathy 25.29 15.26 7 11660 274 46674121
Diabetes mellitus 25.16 15.26 45 11622 50020 46624375
Mucosal membrane hyperplasia 24.87 15.26 5 11662 46 46674349
Dermatitis bullous 24.30 15.26 18 11649 7625 46666770
Altered state of consciousness 23.36 15.26 29 11638 23319 46651076
Lethargy 23.20 15.26 44 11623 51127 46623268
Lipase increased 22.41 15.26 18 11649 8585 46665810
Pruritus 22.09 15.26 119 11548 242233 46432162
Urinary tract infection 21.33 15.26 110 11557 220156 46454239
Parathyroid hyperplasia 20.33 15.26 5 11662 122 46674273
Blood creatinine increased 20.25 15.26 53 11614 76350 46598045
Urine calcium/creatinine ratio increased 19.67 15.26 5 11662 140 46674255
Bite 18.91 15.26 6 11661 378 46674017
Vomiting 18.83 15.26 184 11483 452610 46221785
Insulin-like growth factor decreased 18.74 15.26 6 11661 389 46674006
Mesenteric vein thrombosis 17.86 15.26 7 11660 821 46673574
Albuminuria 17.59 15.26 5 11662 216 46674179
Food refusal 16.23 15.26 5 11662 286 46674109
Pancreatic enzymes increased 15.43 15.26 6 11661 689 46673706
Blood potassium increased 15.27 15.26 20 11647 16947 46657448

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Pemphigoid 420.34 13.69 150 13552 7378 29931398
Pancreatitis 225.92 13.69 163 13539 36327 29902449
Hypoglycaemia 176.02 13.69 162 13540 50819 29887957
Diabetic ketoacidosis 146 13.69 91 13611 15895 29922881
Glycosylated haemoglobin increased 140.37 13.69 74 13628 9417 29929359
Blood glucose increased 134.75 13.69 153 13549 61377 29877399
Dermatitis bullous 88.56 13.69 47 13655 6057 29932719
Euglycaemic diabetic ketoacidosis 81.17 13.69 31 13671 1840 29936936
Blood mercury abnormal 67.97 13.69 16 13686 169 29938607
5-hydroxyindolacetic acid in urine increased 65.95 13.69 16 13686 194 29938582
Cerebral infarction 53.29 13.69 63 13639 26310 29912466
Pancreatic carcinoma 50.67 13.69 36 13666 7801 29930975
Pancreatitis acute 48.02 13.69 59 13643 25636 29913140
Mean platelet volume increased 46.81 13.69 14 13688 389 29938387
Ventricular hyperkinesia 44.85 13.69 12 13690 220 29938556
Mitral valve thickening 44.85 13.69 12 13690 220 29938556
Right atrial enlargement 43.77 13.69 12 13690 242 29938534
Hyperglycaemia 43.30 13.69 66 13636 35134 29903642
Low density lipoprotein decreased 41.64 13.69 16 13686 965 29937811
Acute kidney injury 41.14 13.69 239 13463 273603 29665173
Cardiac failure 40.62 13.69 106 13596 83312 29855464
Hypochromasia 40.21 13.69 12 13690 331 29938445
Ketoacidosis 38.46 13.69 23 13679 3723 29935053
Hepatic neoplasm 37.80 13.69 18 13684 1841 29936935
Left atrial enlargement 36.31 13.69 12 13690 465 29938311
Left ventricular enlargement 33.81 13.69 12 13690 578 29938198
Blood glucose abnormal 33.63 13.69 24 13678 5235 29933541
Necrotising oesophagitis 33.62 13.69 11 13691 413 29938363
Haematocrit increased 30.38 13.69 15 13687 1661 29937115
Pericardial haemorrhage 30.17 13.69 18 13684 2900 29935876
Renal impairment 28.51 13.69 94 13608 84090 29854686
Diabetes mellitus inadequate control 28.31 13.69 32 13670 12730 29926046
Completed suicide 27.41 13.69 6 13696 99486 29839290
Mucosal dryness 27.09 13.69 12 13690 1039 29937737
Drug abuse 27.01 13.69 3 13699 82069 29856707
Expired product administered 25.33 13.69 16 13686 2853 29935923
Neoplasm 24.61 13.69 18 13684 4078 29934698
Glomerular filtration rate decreased 24.37 13.69 28 13674 11334 29927442
Interstitial lung disease 23.85 13.69 71 13631 60126 29878650
Diabetes mellitus 23.29 13.69 56 13646 41809 29896967
Amylase increased 22.94 13.69 20 13682 5821 29932955
Hypervolaemia 22.86 13.69 13 13689 1916 29936860
Haemoglobin increased 22.71 13.69 15 13687 2887 29935889
Chronic kidney disease 22.55 13.69 52 13650 37786 29900990
Toxicity to various agents 22.35 13.69 29 13673 177154 29761622
Urine ketone body present 21.51 13.69 10 13692 969 29937807
Lipase increased 21.39 13.69 23 13679 8653 29930123
Left atrial dilatation 20.91 13.69 12 13690 1799 29936977
Diabetic nephropathy 20.56 13.69 12 13690 1857 29936919
Diabetic ketoacidotic hyperglycaemic coma 20.19 13.69 6 13696 163 29938613
Hypertensive heart disease 20.13 13.69 13 13689 2407 29936369
Red blood cell count decreased 20.09 13.69 40 13662 26281 29912495
Poikilocytosis 19.98 13.69 6 13696 169 29938607
Blood chloride increased 19.58 13.69 13 13689 2522 29936254
Genital infection fungal 19.43 13.69 6 13696 186 29938590
Haemodynamic instability 19.33 13.69 21 13681 7994 29930782
Hyperlactacidaemia 19.26 13.69 13 13689 2593 29936183
Blood phosphorus increased 19.23 13.69 13 13689 2598 29936178
Electrocardiogram T wave inversion 18.99 13.69 12 13690 2142 29936634
Hypohidrosis 18.85 13.69 6 13696 206 29938570
Neutropenia 18.40 13.69 19 13683 128521 29810255
Hypoglycaemic coma 18.12 13.69 12 13690 2319 29936457
Lactic acidosis 17.62 13.69 42 13660 31171 29907605
Bronchitis viral 17.60 13.69 6 13696 256 29938520
Blindness transient 17.48 13.69 11 13691 1948 29936828
Eosinophil count increased 17.02 13.69 19 13683 7454 29931322
High density lipoprotein decreased 16.82 13.69 13 13689 3197 29935579
Blood uric acid increased 16.70 13.69 17 13685 6006 29932770
Drug ineffective 16.53 13.69 90 13612 340297 29598479
Marasmus 16.51 13.69 7 13695 545 29938231
Hypovolaemia 16.46 13.69 20 13682 8585 29930191
Peak expiratory flow rate decreased 16.45 13.69 5 13697 147 29938629
Left ventricular dysfunction 16.30 13.69 20 13682 8671 29930105
Hepatic function abnormal 16.16 13.69 49 13653 41896 29896880
Immune-mediated myositis 16.15 13.69 9 13693 1276 29937500
Skin disorder 16.04 13.69 23 13679 11585 29927191
Urticaria 15.88 13.69 58 13644 54548 29884228
Gastric cancer 15.63 13.69 15 13687 4935 29933841
Femoral neck fracture 15.61 13.69 12 13690 2930 29935846
Rhinalgia 15.14 13.69 6 13696 393 29938383
Electrocardiogram ST segment elevation 15.06 13.69 14 13688 4428 29934348
Drug eruption 15.05 13.69 28 13674 17498 29921278
Dust allergy 14.88 13.69 6 13696 411 29938365
Erythema multiforme 14.37 13.69 18 13684 7967 29930809
Nephrogenic anaemia 14.23 13.69 10 13692 2129 29936647
Blood iron decreased 14.21 13.69 13 13689 4027 29934749
Red cell distribution width increased 14.07 13.69 13 13689 4081 29934695
Haematocrit decreased 13.89 13.69 38 13664 30661 29908115
Aortic valve incompetence 13.84 13.69 14 13688 4909 29933867

Pharmacologic Action:

SourceCodeDescription
ATC A10BD11 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Combinations of oral blood glucose lowering drugs
ATC A10BD19 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Combinations of oral blood glucose lowering drugs
ATC A10BH05 ALIMENTARY TRACT AND METABOLISM
DRUGS USED IN DIABETES
BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS
Dipeptidyl peptidase 4 (DPP-4) inhibitors
MeSH PA D054873 Dipeptidyl-Peptidase IV Inhibitors
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D006728 Hormones
MeSH PA D007004 Hypoglycemic Agents
MeSH PA D054795 Incretins
MeSH PA D011480 Protease Inhibitors
FDA MoA N0000175912 Dipeptidyl Peptidase 4 Inhibitors
FDA EPC N0000175913 Dipeptidyl Peptidase 4 Inhibitor
CHEBI has role CHEBI:35526 hypoglycemic drug
CHEBI has role CHEBI:68612 dpp-4 inhibitor

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Diabetes mellitus type 2 indication 44054006 DOID:9352
Pancreatitis contraindication 75694006 DOID:4989
Hypoglycemic disorder contraindication 237630007

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 9.16 Basic
pKa2 6.13 Basic
pKa3 3.79 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
5MG TRADJENTA BOEHRINGER INGELHEIM N201280 May 2, 2011 RX TABLET ORAL July 3, 2022 INFORMATION ADDED TO THE LABELING TO DESCRIBE CARMELINULL TRIAL TO FULFILL POSTMARKETING COMMITMENT 1766-4
2.5MG;1GM JENTADUETO BOEHRINGER INGELHEIM N201281 Jan. 30, 2012 RX TABLET ORAL July 3, 2022 INFORMATION ADDED TO THE LABELING TO DESCRIBE CARMELINULL TRIAL TO FULFILL POSTMARKETING COMMITMENT 1766-4
2.5MG;500MG JENTADUETO BOEHRINGER INGELHEIM N201281 Jan. 30, 2012 RX TABLET ORAL July 3, 2022 INFORMATION ADDED TO THE LABELING TO DESCRIBE CARMELINULL TRIAL TO FULFILL POSTMARKETING COMMITMENT 1766-4
2.5MG;850MG JENTADUETO BOEHRINGER INGELHEIM N201281 Jan. 30, 2012 RX TABLET ORAL July 3, 2022 INFORMATION ADDED TO THE LABELING TO DESCRIBE CARMELINULL TRIAL TO FULFILL POSTMARKETING COMMITMENT 1766-4
10MG;5MG GLYXAMBI BOEHRINGER INGELHEIM N206073 Jan. 30, 2015 RX TABLET ORAL July 3, 2022 INFORMATION ADDED TO THE LABELING TO DESCRIBE CARMELINULL TRIAL TO FULFILL POSTMARKETING COMMITMENT 1766-4
25MG;5MG GLYXAMBI BOEHRINGER INGELHEIM N206073 Jan. 30, 2015 RX TABLET ORAL July 3, 2022 INFORMATION ADDED TO THE LABELING TO DESCRIBE CARMELINULL TRIAL TO FULFILL POSTMARKETING COMMITMENT 1766-4
2.5MG;1GM JENTADUETO XR BOEHRINGER INGELHEIM N208026 May 27, 2016 RX TABLET, EXTENDED RELEASE ORAL July 3, 2022 INFORMATION ADDED TO THE LABELING TO DESCRIBE CARMELINULL TRIAL TO FULFILL POSTMARKETING COMMITMENT 1766-4
5MG;1GM JENTADUETO XR BOEHRINGER INGELHEIM N208026 May 27, 2016 RX TABLET, EXTENDED RELEASE ORAL July 3, 2022 INFORMATION ADDED TO THE LABELING TO DESCRIBE CARMELINULL TRIAL TO FULFILL POSTMARKETING COMMITMENT 1766-4
5MG TRADJENTA BOEHRINGER INGELHEIM N201280 May 2, 2011 RX TABLET ORAL March 30, 2023 ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME
2.5MG;1GM JENTADUETO BOEHRINGER INGELHEIM N201281 Jan. 30, 2012 RX TABLET ORAL March 30, 2023 ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME
2.5MG;500MG JENTADUETO BOEHRINGER INGELHEIM N201281 Jan. 30, 2012 RX TABLET ORAL March 30, 2023 ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME
2.5MG;850MG JENTADUETO BOEHRINGER INGELHEIM N201281 Jan. 30, 2012 RX TABLET ORAL March 30, 2023 ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME
10MG;5MG GLYXAMBI BOEHRINGER INGELHEIM N206073 Jan. 30, 2015 RX TABLET ORAL March 30, 2023 ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME
25MG;5MG GLYXAMBI BOEHRINGER INGELHEIM N206073 Jan. 30, 2015 RX TABLET ORAL March 30, 2023 ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME
2.5MG;1GM JENTADUETO XR BOEHRINGER INGELHEIM N208026 May 27, 2016 RX TABLET, EXTENDED RELEASE ORAL March 30, 2023 ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME
5MG;1GM JENTADUETO XR BOEHRINGER INGELHEIM N208026 May 27, 2016 RX TABLET, EXTENDED RELEASE ORAL March 30, 2023 ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Dipeptidyl peptidase 4 Enzyme INHIBITOR IC50 10 CHEMBL CHEMBL
Prolyl endopeptidase FAP Enzyme IC50 7.05 CHEMBL
Muscarinic acetylcholine receptor M1 GPCR IC50 6.53 CHEMBL
Dipeptidyl peptidase 9 Enzyme IC50 4 CHEMBL
Prolyl endopeptidase FAP Enzyme IC50 6.43 CHEMBL

External reference:

IDSource
4030725 VUID
N0000182735 NUI
D09566 KEGG_DRUG
4030725 VANDF
C2352547 UMLSCUI
CHEBI:68610 CHEBI
356 PDB_CHEM_ID
CHEMBL237500 ChEMBL_ID
D000069476 MESH_DESCRIPTOR_UI
DB08882 DRUGBANK_ID
10096344 PUBCHEM_CID
6318 IUPHAR_LIGAND_ID
9039 INN_ID
3X29ZEJ4R2 UNII
1100699 RXNORM
181237 MMSL
27861 MMSL
d07767 MMSL
013732 NDDF
702798009 SNOMEDCT_US
703667006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Tradjenta HUMAN PRESCRIPTION DRUG LABEL 1 0597-0140 TABLET, FILM COATED 5 mg ORAL NDA 29 sections
Jentadueto HUMAN PRESCRIPTION DRUG LABEL 2 0597-0146 TABLET, FILM COATED 2.50 mg ORAL NDA 32 sections
Jentadueto HUMAN PRESCRIPTION DRUG LABEL 2 0597-0147 TABLET, FILM COATED 2.50 mg ORAL NDA 32 sections
Jentadueto HUMAN PRESCRIPTION DRUG LABEL 2 0597-0148 TABLET, FILM COATED 2.50 mg ORAL NDA 32 sections
Glyxambi HUMAN PRESCRIPTION DRUG LABEL 2 0597-0164 TABLET, FILM COATED 5 mg ORAL NDA 32 sections
Glyxambi HUMAN PRESCRIPTION DRUG LABEL 2 0597-0182 TABLET, FILM COATED 5 mg ORAL NDA 32 sections
Jentadueto XR HUMAN PRESCRIPTION DRUG LABEL 2 0597-0270 TABLET, FILM COATED, EXTENDED RELEASE 2.50 mg ORAL NDA 32 sections
Jentadueto XR HUMAN PRESCRIPTION DRUG LABEL 2 0597-0275 TABLET, FILM COATED, EXTENDED RELEASE 5 mg ORAL NDA 32 sections
Trijardy XR HUMAN PRESCRIPTION DRUG LABEL 3 0597-0380 TABLET, EXTENDED RELEASE 5 mg ORAL NDA 34 sections
Trijardy XR HUMAN PRESCRIPTION DRUG LABEL 3 0597-0385 TABLET, EXTENDED RELEASE 2.50 mg ORAL NDA 34 sections
Trijardy XR HUMAN PRESCRIPTION DRUG LABEL 3 0597-0390 TABLET, EXTENDED RELEASE 5 mg ORAL NDA 34 sections
Trijardy XR HUMAN PRESCRIPTION DRUG LABEL 3 0597-0395 TABLET, EXTENDED RELEASE 2.50 mg ORAL NDA 34 sections
Tradjenta HUMAN PRESCRIPTION DRUG LABEL 1 50090-4383 TABLET, FILM COATED 5 mg ORAL NDA 29 sections
Jentadueto HUMAN PRESCRIPTION DRUG LABEL 2 54868-6461 TABLET, FILM COATED 2.50 mg ORAL NDA 28 sections
Tradjenta HUMAN PRESCRIPTION DRUG LABEL 1 55154-0410 TABLET, FILM COATED 5 mg ORAL NDA 29 sections
Jentadueto HUMAN PRESCRIPTION DRUG LABEL 2 63629-6524 TABLET, FILM COATED 2.50 mg ORAL NDA 31 sections