Details of the Drug Combination

General Information of Drug Combination (ID: DC5KBFV)

• Drug Combination Name: Saxagliptin + Exenatide
• Indication: Prediabetes; Status: Phase 4 [1]
• Component Drugs:
  Saxagliptin (DMGXENV): Small molecular drug
  Exenatide (DMYHBKN): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Saxagliptin

Disease Entry	ICD 11	Status	REF
Type-2 diabetes	5A11	Approved	[2]

Saxagliptin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dipeptidyl peptidase 4 (DPP-4)	TTDIGC1	DPP4_HUMAN	Inhibitor	[6]

Saxagliptin Interacts with 4 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[7]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 4C1 (SLCO4C1)	DTY0QMU	SO4C1_HUMAN	Substrate	[9]

Saxagliptin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[10]

Saxagliptin Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Dipeptidyl peptidase 4 (DPP4)	OT16MVL9	DPP4_HUMAN	Decreases Activity	[11]

Indication(s) of Exenatide

Disease Entry	ICD 11	Status	REF
Inflammation	1A00-CA43.1	Approved	[3]
Non-insulin dependent diabetes	5A11	Approved	[3]
Type-1/2 diabetes	5A10-5A11	Approved	[3]
Type-2 diabetes	5A11	Approved	[4]
Cardiovascular disease	BA00-BE2Z	Phase 3	[5]

Exenatide Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Glucagon-like peptide 1 receptor (GLP1R)	TTVIMDE	GLP1R_HUMAN	Binder	[12]

Exenatide Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Dipeptidyl peptidase IV (DPP4)	DEKZQY6	DPP4_HUMAN	Metabolism	[13]

Exenatide Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[14]

References

• [1] ClinicalTrials.gov (NCT02104739) Effects of Antidiabetic Medications on the Postprandial State in Prediabetes
• [2] 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: 6316).
• [3] Exenatide FDA Label
• [4] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [7] Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet. 2010 Sep;49(9):573-88.
• [8] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [9] Comparative clinical pharmacokinetics of dipeptidyl peptidase-4 inhibitors. Clin Pharmacokinet. 2012 Aug 1;51(8):501-14.
• [10] Effect of rifampicin on the pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor, in healthy subjects. Br J Clin Pharmacol. 2011 Jul;72(1):92-102.
• [11] Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV. J Med Chem. 2011 Jan 27;54(2):510-24.
• [12] Improved glycemic control and reduction of cardiometabolic risk factors in subjects with type 2 diabetes and metabolic syndrome treated with exenatide in a clinical practice setting. Diabetes TechnolTher. 2009 Jun;11(6):353-9.
• [13] In vitro metabolic stability of exendin-4: pharmacokinetics and identification of cleavage products. PLoS One. 2015 Feb 27;10(2):e0116805.
• [14] Biochemical, pharmaceutical and therapeutic properties of long-acting lithocholic acid derivatized exendin-4 analogs. J Control Release. 2010 Mar 3;142(2):206-13. doi: 10.1016/j.jconrel.2009.10.025. Epub 2009 Nov 10.