Details of the Drug Combination

General Information of Drug Combination (ID: DC4AIRB)

• Drug Combination Name: Linagliptin + Glipizide
• Indication: Chronic Kidney Diseases; Status: Phase 1 [1]
• Component Drugs:
  Linagliptin (DMWFJTR): Small molecular drug
  Glipizide (DMZA5PQ): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Linagliptin

Disease Entry	ICD 11	Status	REF
Non-insulin dependent diabetes	5A11	Approved	[2]
Type 2 diabetes	5A11	Approved	[3]
Type-2 diabetes	5A11	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[5]

Linagliptin Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dipeptidyl peptidase 4 (DPP-4)	TTDIGC1	DPP4_HUMAN	Inhibitor	[7]
HUMAN dipeptidyl peptidase 4 (DPP-4)	TTF928K	DPP4_HUMAN	Inhibitor	[8]

Linagliptin Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

Indication(s) of Glipizide

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Approved	[6]

Glipizide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Inward rectifier potassium channel Kir1.2 (KCNJ10)	TTG140O	KCJ10_HUMAN	Blocker	[10]

Glipizide Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	DTJ0EW4	ABCBB_HUMAN	Substrate	[11]

Glipizide Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[12]
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[13]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[14]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[15]

Glipizide Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[11]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[16]
Aldo-keto reductase family 1 member C2 (AKR1C2)	OTQ2XMO3	AK1C2_HUMAN	Decreases Activity	[16]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Decreases Activity	[16]
Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4)	OTJZG0LD	GLUT4_HUMAN	Increases ADR	[17]

References

• [1] ClinicalTrials.gov (NCT02608177) Continuous Glucose Monitoring to Assess Glycemia in Chronic Kidney Disease - Changing Glucose Management
• [2] Linagliptin FDA Label
• [3] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 208026
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6318).
• [5] ClinicalTrials.gov (NCT04371978) Efficacy and Safety of Dipeptidyl Peptidase-4 Inhibitors in Diabetic Patients With Established COVID-19. U.S. National Institutes of Health.
• [6] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6821).
• [7] Boehringer Ingelheim. Product Development Pipeline. June 2 2009.
• [8] DPP4 inhibition: preventing SARS-CoV-2 infection and/or progression of COVID-19 Diabetes Metab Res Rev. 2020 Apr 26.
• [9] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [10] Triggering and amplification of insulin secretion by dimethyl alpha-ketoglutarate, a membrane permeable alpha-ketoglutarate analogue. Eur J Pharmacol. 2009 Apr 1;607(1-3):41-6.
• [11] Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
• [12] Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus. Pharmacoeconomics. 2004;22(6):389-411.
• [13] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [14] Clinical consequences of cytochrome P450 2C9 polymorphisms. Clin Pharmacol Ther. 2005 Jan;77(1):1-16.
• [15] Pharmacokinetics of chlorpheniramine, phenytoin, glipizide and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics. 1999 Feb;9(1):71-80.
• [16] Initro inhibition of AKR1Cs by sulphonylureas and the structural basis. Chem Biol Interact. 2015 Oct 5;240:310-5.
• [17] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.