Details of the Drug Combination

General Information of Drug Combination (ID: DCY47RE)

• Drug Combination Name: Sitagliptin + Insulin-glargine
• Indication: Type 2 Diabetes; Status: Phase 4 [1]
• Component Drugs:
  Sitagliptin (DMGDKXN): Small molecular drug
  Insulin-glargine (DMR4HIW): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Sitagliptin

Disease Entry	ICD 11	Status	REF
Cystic fibrosis	CA25	Approved	[2]
Non-insulin dependent diabetes	5A11	Approved	[2]
Renal hypoplasia	N.A.	Approved	[2]
Type-2 diabetes	5A11	Approved	[3]
Peripheral arterial disease	BD4Z	Phase 1/2	[4]

Sitagliptin 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	[10]

Sitagliptin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[12]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[13]

Sitagliptin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[14]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[14]

Indication(s) of Insulin-glargine

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Approved	[5]
Non-insulin dependent diabetes	5A11	Approved	[6]
Malaria	1F40-1F45	Phase 3	[7]
Type-1 diabetes	5A10	Phase 3	[8]
Type-2 diabetes	5A11	Application submitted	[9]

Insulin-glargine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Insulin (INS)	TTZOPHG	INS_HUMAN	Modulator	[15]

Insulin-glargine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Insulin receptor (INSR)	OTTY341H	INSR_HUMAN	Increases Phosphorylation	[16]
Insulin-like growth factor 1 receptor (IGF1R)	OTXJIF13	IGF1R_HUMAN	Increases Phosphorylation	[16]

References

• [1] ClinicalTrials.gov (NCT01845831) Sitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes
• [2] Sitagliptin 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: 6286).
• [4] ClinicalTrials.gov (NCT01619332) Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763. U.S. National Institutes of Health.
• [5] 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: 7572).
• [6] Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022 Feb 8;327(6):534-545.
• [7] ClinicalTrials.gov (NCT02059161) A Study of the Safety and Efficacy of MK-1293 Compared to Lantus in Participants With Type 1 Diabetes Mellitus (T1DM) (MK-1293-003). U.S. National Institutes of Health.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [10] Novel therapeutics for type 2 diabetes: incretin hormone mimetics (glucagon-like peptide-1 receptor agonists) and dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2009 Oct;124(1):113-38.
• [11] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [12] 265 effect of dietary cholesterol on gallbladder bile lithogenicity and gene expression in the enterohepatic axis of non-obese gallstone and control women. Journal of Hepatology, 2009, 50(09):S105-S106.
• [13] Transport of the dipeptidyl peptidase-4 inhibitor sitagliptin by human organic anion transporter 3, organic anion transporting polypeptide 4C1, and multidrug resistance P-glycoprotein. J Pharmacol Exp Ther. 2007 May;321(2):673-83.
• [14] Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [16] IR and IGF-1R expression affects insulin induced proliferation and DNA damage. Toxicol In Vitro. 2017 Mar;39:68-74. doi: 10.1016/j.tiv.2016.11.011. Epub 2016 Nov 22.