Details of the Drug Combination

General Information of Drug Combination (ID: DC0AML7)

• Drug Combination Name: Liraglutide + Exenatide
• Indication: Diabetes; Status: Phase 1 [1]
• Component Drugs:
  Liraglutide (DM3FXPS): Small molecular drug
  Exenatide (DMYHBKN): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Liraglutide

Disease Entry	ICD 11	Status	REF
Non-insulin dependent diabetes	5A11	Approved	[2]
Type-2 diabetes	5A11	Approved	[3]
Obesity	5B81	Phase 2	[3]

Liraglutide 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	Agonist	[5]

Liraglutide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Dipeptidyl peptidase IV (DPP4)	DEKZQY6	DPP4_HUMAN	Metabolism	[7]
Neprilysin (MME)	DEVN830	NEP_HUMAN	Metabolism	[7]

Liraglutide Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Expression	[8]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Increases Expression	[8]
Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33)	OTRZVI77	ADA33_HUMAN	Increases Expression	[8]

Indication(s) of Exenatide

Disease Entry	ICD 11	Status	REF
Inflammation	1A00-CA43.1	Approved	[4]
Non-insulin dependent diabetes	5A11	Approved	[4]
Type-1/2 diabetes	5A10-5A11	Approved	[4]
Type-2 diabetes	5A11	Approved	[5]
Cardiovascular disease	BA00-BE2Z	Phase 3	[6]

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	[9]

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	[10]

Exenatide Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[11]

References

• [1] ClinicalTrials.gov (NCT01676116) The Efficacy of Insulin Degludec/Liraglutide in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and OAD Therapy
• [2] Liraglutide FDA Label
• [3] 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: 1133).
• [4] Exenatide FDA Label
• [5] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Metabolism and excretion of the once-daily human glucagon-like peptide-1 analog liraglutide in healthy male subjects and its in vitro degradation by dipeptidyl peptidase IV and neutral endopeptidase. Drug Metab Dispos. 2010 Nov;38(11):1944-53.
• [8] Antitumoral activity of liraglutide, a new DNMT inhibitor in breast cancer cells in vitro and in vivo. Chem Biol Interact. 2021 Nov 1;349:109641. doi: 10.1016/j.cbi.2021.109641. Epub 2021 Sep 14.
• [9] 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.
• [10] In vitro metabolic stability of exendin-4: pharmacokinetics and identification of cleavage products. PLoS One. 2015 Feb 27;10(2):e0116805.
• [11] 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.