Linagliptin

Summary

Linagliptin (CHEMBL237500) is an approved small-molecule EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor (ATC A10BH05) targeting DPP4; indicated across 11 conditions including diabetes mellitus and type 2 diabetes mellitus.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A10BH05
• Targets: 1 (DPP4)
• Indications: 11 conditions
• Clinical trials: 149
• Chemistry: 472.5 Da · C25H28N8O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL237500
Name	Linagliptin
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	10096344
ChEBI	CHEBI:68610
ATC	A10BH05
Molecular formula	C25H28N8O2
Molecular weight	472.5
InChIKey	LTXREWYXXSTFRX-QGZVFWFLSA-N

SMILES: CC#CCN1C2=C(N=C1N3CCC[C@H](C3)N)N(C(=O)N(C2=O)CC4=NC5=CC=CC=C5C(=N4)C)C

IUPAC name: 8-[(3R)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]purine-2,6-dione

ChEBI definition: A xanthine that is 7H-xanthine bearing (4-methylquinazolin-2-yl)methyl, methyl, but-2-yn-1-yl and 3-aminopiperidin-1-yl substituents at positions 1, 3, 7 and 8 respectively (the R-enantiomer). Used for treatment of type II diabetes.

Pharmacological roles (ChEBI): EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor, hypoglycemic agent.

Also known as: BI 1356, BI 1356 BS, BI-1356, BI-1356BS, BI1356, BS 1356 BS, Linagliptin, Linagliptin component of glyxambi, Linagliptin component of jentadueto, Linagliptin component of trijardy xr, Linagliptina, Linagliptine

Patent coverage: 2,061 distinct patent families (5,282 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 5,212 (99%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
DPP4	dipeptidyl peptidase 4	Inhibition	9	0%	P27487

Broader ChEMBL bioactivity targets: 14 (assay-derived). Sample: Histamine H2 receptor, Muscarinic acetylcholine receptor M1, Muscarinic acetylcholine receptor M3, Adenosine receptor A3, Melanocortin receptor 4, Dipeptidyl peptidase 4, POU domain, class 2, transcription factor 2, POU domain, class 2, transcription factor 1, Dipeptidyl peptidase 4, Growth hormone secretagogue receptor type 1.

Bioactivity

ChEMBL activities: 43 potent at pChembl ≥ 5 of 51 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
DPP4	10	IC50	0.1	nM	CHEMBL_ACT_16609232
DPP4	10	IC50	0.1	nM	CHEMBL_ACT_8038718
P28843	9.92	IC50	0.12	nM	CHEMBL_ACT_25636172
DPP4	9.85	IC50	0.14	nM	CHEMBL_ACT_25636154
DPP4	9.68	IC50	0.21	nM	CHEMBL_ACT_27715997
DPP4	9.4	IC50	0.4	nM	CHEMBL_ACT_24967495
DPP4	9	IC50	1	nM	CHEMBL_ACT_12044048
DPP4	9	IC50	1	nM	CHEMBL_ACT_12588800
DPP4	9	IC50	1	nM	CHEMBL_ACT_13317273
DPP4	9	IC50	1	nM	CHEMBL_ACT_15714327
DPP4	9	IC50	1	nM	CHEMBL_ACT_17739788
DPP4	9	IC50	1	nM	CHEMBL_ACT_17763476
DPP4	9	IC50	1	nM	CHEMBL_ACT_19442622
DPP4	9	IC50	1	nM	CHEMBL_ACT_2008909
DPP4	9	IC50	1	nM	CHEMBL_ACT_2171489
DPP4	9	IC50	1	nM	CHEMBL_ACT_24959144
DPP4	9	IC50	1	nM	CHEMBL_ACT_25636108
DPP4	9	IC50	1	nM	CHEMBL_ACT_25636166
DPP4	9	IC50	1	nM	CHEMBL_ACT_26036393
DPP4	9	IC50	1	nM	CHEMBL_ACT_26768999
DPP4	9	IC50	1	nM	CHEMBL_ACT_27336662
DPP4	8.9	IC50	1.25	nM	CHEMBL_ACT_19149788
DPP4	8.9	IC50	1.25	nM	CHEMBL_ACT_25050690
DPP4	8.7	IC50	2	nM	CHEMBL_ACT_13322387
DPP4	8.7	IC50	2	nM	CHEMBL_ACT_14590259
DPP4	8.7	IC50	2	nM	CHEMBL_ACT_15714184
DPP4	8.7	IC50	2	nM	CHEMBL_ACT_18314058
DPP4	8.51	EC50	3.1	nM	CHEMBL_ACT_25636111
DPP4	8.28	Kd	5.3	nM	CHEMBL_ACT_19442668
DPP4	7.81	IC50	15.37	nM	CHEMBL_ACT_29091144

Target pathways

Aggregated over 1 target gene(s): DPP4.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)	1	DPP4
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)	1	DPP4

Dominant GO biological processes

GO term	Targets
behavioral fear response	1
response to hypoxia	1
proteolysis	1
cell adhesion	1
positive regulation of cell population proliferation	1
negative regulation of extracellular matrix disassembly	1
peptide hormone processing	1
receptor-mediated endocytosis of virus by host cell	1
T cell costimulation	1
regulation of cell-cell adhesion mediated by integrin	1
locomotory exploration behavior	1
psychomotor behavior	1
T cell activation	1
endothelial cell migration	1
symbiont entry into host cell	1

Indications & clinical

Indications

11 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
diabetes mellitus	4	MONDO:0005015	EFO:0000400
type 2 diabetes mellitus	4	MONDO:0005148	MONDO:0005148
respiratory system disorder	3	MONDO:0005087	EFO:0000684
severe acute respiratory syndrome	3	MONDO:0005091	MONDO:0100096
gastric adenocarcinoma	1	MONDO:0005036	EFO:0000503
hypertensive disorder	1	MONDO:0005044	EFO:0000537
non-small cell lung carcinoma	1	MONDO:0005233	EFO:0003060
carcinoma of esophagus	1	MONDO:0019086	EFO:0002916
kidney failure	1	MONDO:0001106	HP:0000083
adenocarcinoma	1	MONDO:0004970	MONDO:0003219

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 149.

Phase distribution

Phase	Trials
PHASE1	45
PHASE3	44
PHASE4	37
Not specified	17
PHASE2	4
PHASE1/PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06449833	PHASE4	RECRUITING	Effect of Henagliflozein on Hepatic Fat Content in Patients With T2DM and NAFLD
NCT06851962	PHASE4	ACTIVE_NOT_RECRUITING	Impact of Pharmacogenetic-Guided Treatment on Type 2 Diabetes.
NCT06862739	PHASE4	RECRUITING	Glycemic Control With Triple Pathway Approach Through Empagliflozin, Linagliptin and Metformin Combination
NCT07019012	PHASE4	RECRUITING	Cofrogliptin Once Every 2 Weeks as Add-on Therapy to Metformin and Dapagliflozin Versus Daily Linagliptin in Patients With Type 2 Diabetes.
NCT07442006	PHASE4	RECRUITING	Glycemic Variability of Combination Therapies in T2DM
NCT07452913	PHASE4	ENROLLING_BY_INVITATION	Metformin, Empagliflozin With Sitagliptin vs Linagliptin in Type 2 Diabetes
NCT01438814	PHASE4	COMPLETED	Linagliptin in Combination With Metformin in Treatment Naive Patients With Type 2 Diabetes Mellitus and Insufficient Glycaemic Control
NCT01512979	PHASE4	COMPLETED	Linagliptin and Metformin Versus Linagliptin in Newly Diagnosed, Untreated Type 2 Diabetes
NCT01547104	PHASE4	UNKNOWN	Effect of Linagliptin in Comparison With Glimepiride as Add on to Metformin on Postprandial Beta Cell Function, Postprandial Metabolism and Oxidative Stress in Patients With Type 2 Diabetes Mellitus
NCT01617824	PHASE4	COMPLETED	Rapid Effects Linagliptin on Monocyte Polarization and Endothelial Progenitor Cells in Type 2 Diabetes
NCT01897532	PHASE4	COMPLETED	Cardiovascular and Renal Microvascular Outcome Study With Linagliptin in Patients With Type 2 Diabetes Mellitus (CARMELINA)
NCT01903070	PHASE4	COMPLETED	Effects of Linagliptin on Active GLP-1 Concentrations in Subjects With Renal Impairment
NCT01969084	PHASE4	COMPLETED	The Effect of Linagliptin on Mitochondrial and Endothelial Function
NCT02004366	PHASE4	COMPLETED	Linagliptin Inpatient Trial
NCT02061969	PHASE4	COMPLETED	ADA Linagliptin in Long Term Care
NCT02072096	PHASE4	TERMINATED	A Comparison of Two Treatment Strategies in Older Participants With Type 2 Diabetes Mellitus (T2DM)
NCT02092597	PHASE4	COMPLETED	Safety Evaluation of Adverse Reactions in Diabetes
NCT02097342	PHASE4	UNKNOWN	Effect of Linagliptin on Insulin Sensitivity and Pancreatic Beta Cell Function in Patients With Type 2 Diabetes Mellitus
NCT02180334	PHASE4	COMPLETED	The Effect of Combination of Mosapride and DPP-4 Inhibitor on Plasma Concentration of Incretin Hormones
NCT02240680	PHASE4	COMPLETED	Linagliptin as Add on to Basal Insulin in the Elderly
NCT02280174	PHASE4	UNKNOWN	Effect of Linagliptin on TRL Metabolism
NCT02350478	PHASE4	COMPLETED	Effects of Linagliptin on Endothelial Function
NCT02372630	PHASE4	COMPLETED	The Effect of LINAGLIPTIN on Inflammation, Oxidative Stress and Insulin Resistance in Obese Type 2 Diabetes Subjects
NCT02401880	PHASE4	COMPLETED	Effects of Linagliptin in Addition to Empagliflozin on Islet Cell Physiology
NCT02429232	PHASE4	UNKNOWN	A One-year Randomized Controlled Trial Evaluating the Impact of Pioglitazone Versus Linagliptin on Bone Turnover Markers
NCT02442817	PHASE4	COMPLETED	Linagliptin and Mesenchymal Stem Cells: A Pilot Study
NCT02467478	PHASE4	COMPLETED	Linagliptin’s Effect on CD34+ Stem Cells
NCT02768220	PHASE4	WITHDRAWN	The Effect of Sodium-Glucose Cotransporter 2 Inhibitors on Advanced Glycation End Products
NCT02974504	PHASE4	COMPLETED	Phase IV Clinical Trial to Investigate the Effect on Blood Glucose of Evogliptin in Patients With Type 2 Diabetes(EVERGREEN)
NCT03004612	PHASE4	COMPLETED	Effect of Linagliptin + Metformin vs Metformin Alone in Patients With Prediabetes
NCT03011177	PHASE4	COMPLETED	Teneligliptin Versus Linagliptin in Diabetes Mellitus Type Two Patients
NCT03320031	PHASE4	UNKNOWN	A Study of Adding Linagliptin to Control Glycemic Variability and HbA1c in Peritoneal Dialysis Patients With Type 2 Diabetes(PDPD) With Premixed Insulin Therapy
NCT03504566	PHASE4	WITHDRAWN	Rotation for Optimal Targeting of Albuminuria and Treatment Evaluation (ROTATE-2)
NCT03642184	PHASE4	TERMINATED	Efficacy and Safety of Empagliflozin in NODAT
NCT04088461	PHASE4	COMPLETED	Effect of Linagliptin + Metformin on Patients Who do Not Achieve Normoglucemia With Metformine
NCT04341935	PHASE4	WITHDRAWN	Effects of DPP4 Inhibition on COVID-19
NCT05200793	PHASE4	UNKNOWN	Efficacy of Empagliflozin or Linagliptin as an Alternative to Metformin for Treatment of Polycystic Ovary Syndrome
NCT04670666	PHASE3	RECRUITING	Efficacy and Safety of Madalena Association in the Treatment of Type II Diabetes Mellitus
NCT05886088	PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of LID104 in the Treatment of Type II Diabetes Mellitus
NCT00601250	PHASE3	COMPLETED	Efficacy and Safety of B I1356 (Linagliptin) vs. Placebo Added to Metformin Background Therapy in Patients With Type 2 Diabetes

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 14 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

28 molecules share ≥1 primary target. Top 28 by shared-target count:

Molecule	Source	Status	Shared targets
ALOGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	DPP4
SAXAGLIPTIN	ChEMBL + PubChem	Phase 4 (approved)	DPP4
ANAGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
EVOGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
GEMIFLOXACIN	ChEMBL	Phase 4 (approved)	DPP4
GOSOGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
METFORMIN	ChEMBL	Phase 4 (approved)	DPP4
OMARIGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
SITAGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
TENELIGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
TRELAGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
VIDARABINE	ChEMBL	Phase 4 (approved)	DPP4
VILDAGLIPTIN	ChEMBL	Phase 4 (approved)	DPP4
CAFFEIC ACID	ChEMBL	Phase 3	DPP4
DBPR-108	ChEMBL	Phase 3	DPP4
DUTOGLIPTIN	ChEMBL	Phase 3	DPP4
EPIGALOCATECHIN GALLATE	ChEMBL	Phase 3	DPP4
QUERCETIN	ChEMBL	Phase 3	DPP4
RESVERATROL	ChEMBL	Phase 3	DPP4
RETAGLIPTIN	ChEMBL	Phase 3	DPP4
TALABOSTAT	ChEMBL	Phase 3	DPP4
CARMEGLIPTIN	ChEMBL	Phase 2	DPP4
COFROGLIPTIN	ChEMBL	Phase 2	DPP4
FLAVONE	ChEMBL	Phase 2	DPP4
GALLIC ACID	ChEMBL	Phase 2	DPP4
GENISTEIN	ChEMBL	Phase 2	DPP4
LUTEOLIN	ChEMBL	Phase 2	DPP4
Carfilzomib	PubChem	Approved	DPP4