Details of the Drug Combination

General Information of Drug Combination (ID: DCPQ5DJ)

• Drug Combination Name: Insulin-lispro + Sitagliptin
• Indication: Type 2 Diabetes; Status: Phase 4 [1]
• Component Drugs:
  Insulin-lispro (DM4O90W): Small molecular drug
  Sitagliptin (DMGDKXN): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Insulin-lispro

Disease Entry	ICD 11	Status	REF
Diabetic complication	5A2Y	Approved	[2]
Non-insulin dependent diabetes	5A11	Approved	[3]
Type-1 diabetes	5A10	Approved	[4]

Insulin-lispro Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Insulin receptor (INSR)	TTCBFJO	INSR_HUMAN	Binder	[8]

Indication(s) of Sitagliptin

Disease Entry	ICD 11	Status	REF
Cystic fibrosis	CA25	Approved	[5]
Non-insulin dependent diabetes	5A11	Approved	[5]
Renal hypoplasia	N.A.	Approved	[5]
Type-2 diabetes	5A11	Approved	[6]
Peripheral arterial disease	BD4Z	Phase 1/2	[7]

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	[9]

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	[10]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[11]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[12]

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	[13]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[13]

References

• [1] ClinicalTrials.gov (NCT05579119) SITAgliptin Plus GLARgine to Glycemic Control in the Hospital Setting (SITAGLAR-H)
• [2] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [3] Diabetes mellitus: complications and therapeutics. Med Sci Monit. 2006 Jul;12(7):RA130-47. Epub 2006 Jun 28.
• [4] Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes. N Engl J Med. 2022 Sep 29;387(13):1161-1172.
• [5] Sitagliptin FDA Label
• [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: 6286).
• [7] ClinicalTrials.gov (NCT01619332) Clinical Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LEZ763. U.S. National Institutes of Health.
• [8] Hope for insulin mimetic oral antidiabetic drugs. Eur J Endocrinol. 1999 Dec;141(6):561-2.
• [9] 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.
• [10] Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
• [11] 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.
• [12] 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.
• [13] Pharmacokinetics of dipeptidylpeptidase-4 inhibitors. Diabetes Obes Metab. 2010 Aug;12(8):648-58.