Details of the Drug Combination

General Information of Drug Combination (ID: DCHEELX)

• Drug Combination Name: Liraglutide + Empagliflozin
• Indication: Diabetes Mellitus, Type 2; Status: Phase 1 [1]
• Component Drugs:
  Liraglutide (DM3FXPS): Small molecular drug
  Empagliflozin (DMRF9YK): 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	[6]
Neprilysin (MME)	DEVN830	NEP_HUMAN	Metabolism	[6]

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	[7]
Cadherin-1 (CDH1)	OTFJMXPM	CADH1_HUMAN	Increases Expression	[7]
Disintegrin and metalloproteinase domain-containing protein 33 (ADAM33)	OTRZVI77	ADA33_HUMAN	Increases Expression	[7]

Indication(s) of Empagliflozin

Disease Entry	ICD 11	Status	REF
Type-1 diabetes	5A10	Approved	[4]

Empagliflozin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Sodium/glucose cotransporter 2 (SGLT2)	TTLWPVF	SC5A2_HUMAN	Modulator	[8]

Empagliflozin Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]

Empagliflozin Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[11]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[11]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[11]
UDP-glucuronosyltransferase 1A8 (UGT1A8)	DE2GB8N	UD18_HUMAN	Metabolism	[11]

References

• [1] ClinicalTrials.gov (NCT03993132) A Study Using Medical Records of Danish People With Type 2 Diabetes Comparing Empagliflozin and Glucagon-Like Peptide-1 Receptor Agonists (GLP1-RA) in the Occurrence of Serious Cardiovascular Outcomes
• [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] 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: 4754).
• [5] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [6] 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.
• [7] 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.
• [8] 2014 FDA drug approvals. Nat Rev Drug Discov. 2015 Feb;14(2):77-81.
• [9] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01665)
• [10] KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017 Jan 4;45(D1):D353-D361. (dg:DG01913)
• [11] Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes. P T. 2015 Jun;40(6):364-8.