semaglutide Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
Glucagon-like Peptide (GLP) analogues	5267	910463-68-2

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: semaglutide NNC 0113-0217 ozempic	Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors. The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilized against degradation by the DPP-4 enzyme. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase. Molecular weight: 4113.64 Formula: C187H291N45O59 CLOGP: LIPINSKI: None HAC: 104 HDO: 57 TPSA: 1646.18 ALOGS: ROTB: 149

Molecule

Description

Molfile Inchi Smiles

Synonyms:

semaglutide
NNC 0113-0217
ozempic

Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. GLP-1 is a physiological hormone that has multiple actions on glucose, mediated by the GLP-1 receptors. The principal mechanism of protraction resulting in the long half-life of semaglutide is albumin binding, which results in decreased renal clearance and protection from metabolic degradation. Furthermore, semaglutide is stabilized against degradation by the DPP-4 enzyme. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Thus, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase.

Molecular weight: 4113.64
Formula: C187H291N45O59
CLOGP:
LIPINSKI: None
HAC: 104
HDO: 57
TPSA: 1646.18
ALOGS:
ROTB: 149

Drug dosage:

Dose	Unit	Route
0.11	mg	P

ADMET properties:

None

Approvals:

Date	Agency	Company
Feb. 8, 2018	EMA	Novo Nordisk A/S
March 23, 2018	PMDA	Novo Nordisk Pharma Ltd
Dec. 5, 2017	FDA	NOVO NORDISK INC

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Nausea	245.22	52.60	95	367	112094	2245529
Vomiting	173.59	52.60	66	396	71536	2286087
Pancreatitis	154.65	52.60	37	425	8042	2349581
Diabetic ketoacidosis	66.18	52.60	16	446	3548	2354075

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Nausea	260.27	50.57	93	384	51103	1695201
Vomiting	186.83	50.57	68	409	38247	1708057
Diarrhoea	150.61	50.57	64	413	53788	1692516
Pancreatitis	124.99	50.57	34	443	7153	1739151
Weight decreased	72.54	50.57	30	447	22723	1723581
Inappropriate schedule of product administration	57.93	50.57	19	458	7440	1738864
Eructation	53.41	50.57	11	466	682	1745622

Pharmacologic Action:

Source	Code	Description
ATC	A10BJ06	ALIMENTARY TRACT AND METABOLISM DRUGS USED IN DIABETES BLOOD GLUCOSE LOWERING DRUGS, EXCL. INSULINS Glucagon-like peptide-1 (GLP-1) analogues
FDA EPC	N0000178480	GLP-1 Receptor Agonist
FDA CS	M0160181	Glucagon-Like Peptide 1
FDA MoA	N0000020058	Glucagon-like Peptide-1 (GLP-1) Agonists

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Diabetes mellitus type 2	indication	44054006	DOID:9352

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.23	acidic
pKa2	3.31	acidic
pKa3	3.71	acidic
pKa4	3.97	acidic
pKa5	4.22	acidic
pKa6	4.53	acidic
pKa7	4.76	acidic
pKa8	9.65	acidic
pKa9	12.06	acidic
pKa10	12.28	acidic
pKa11	12.41	acidic
pKa12	12.5	acidic
pKa13	12.63	acidic
pKa14	12.76	acidic
pKa15	12.95	acidic
pKa16	12.98	acidic
pKa17	13.11	acidic
pKa18	13.18	acidic
pKa19	13.24	acidic
pKa20	13.3	acidic
pKa21	13.4	acidic
pKa22	13.51	acidic
pKa23	13.61	acidic
pKa24	13.66	acidic
pKa25	13.73	acidic
pKa26	13.77	acidic
pKa27	13.83	acidic
pKa28	13.87	acidic
pKa29	13.94	acidic
pKa30	11.05	Basic
pKa31	10.45	Basic
pKa32	7.88	Basic
pKa33	5.98	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
2MG/1.5ML (1.34MG/ML)	OZEMPIC	NOVO	N209637	Dec. 5, 2017	RX	SOLUTION	SUBCUTANEOUS	8536122	March 20, 2026	OZEMPIC IS INDICATED AS AN ADJUNCT TO DIET AND EXERCISE TO IMPROVE GLYCEMIC CONTROL IN ADULTS WITH TYPE 2 DIABETES MELLITUS
14MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	8536122	March 20, 2026	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
3MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	8536122	March 20, 2026	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
7MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	8536122	March 20, 2026	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
2MG/1.5ML (1.34MG/ML)	OZEMPIC	NOVO	N209637	Dec. 5, 2017	RX	SOLUTION	SUBCUTANEOUS	8129343	Jan. 29, 2029	OZEMPIC IS INDICATED AS AN ADJUNCT TO DIET AND EXERCISE TO IMPROVE GLYCEMIC CONTROL IN ADULTS WITH TYPE 2 DIABETES MELLITUS
14MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	8129343	Jan. 29, 2029	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
3MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	8129343	Jan. 29, 2029	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
7MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	8129343	Jan. 29, 2029	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
14MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	9278123	Dec. 16, 2031	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
3MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	9278123	Dec. 16, 2031	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
7MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	9278123	Dec. 16, 2031	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
2MG/1.5ML (1.34MG/ML)	OZEMPIC	NOVO	N209637	Dec. 5, 2017	RX	SOLUTION	SUBCUTANEOUS	10335462	June 21, 2033	A METHOD OF TREATING TYPE 2 DIABETES COMPRISING ADMINISTERING SEMAGLUTIDE ONCE WEEKLY IN A AMOUNT OF 1.0 MG TO A SUBJECT IN NEED THEREOF
14MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	10278923	May 2, 2034	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
3MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	10278923	May 2, 2034	METHOD OF TREATING TYPE 2 DIABETES MELLITUS
7MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	10278923	May 2, 2034	METHOD OF TREATING TYPE 2 DIABETES MELLITUS

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
14MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	Sept. 20, 2022	NEW PRODUCT
3MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	Sept. 20, 2022	NEW PRODUCT
7MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	Sept. 20, 2022	NEW PRODUCT
2MG/1.5ML (1.34MG/ML)	OZEMPIC	NOVO	N209637	Dec. 5, 2017	RX	SOLUTION	SUBCUTANEOUS	Dec. 5, 2022	NEW CHEMICAL ENTITY
14MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	Dec. 5, 2022	NEW CHEMICAL ENTITY
3MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	Dec. 5, 2022	NEW CHEMICAL ENTITY
7MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	Dec. 5, 2022	NEW CHEMICAL ENTITY
2MG/1.5ML (1.34MG/ML)	OZEMPIC	NOVO	N209637	Dec. 5, 2017	RX	SOLUTION	SUBCUTANEOUS	Jan. 16, 2023	REDUCE THE RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS (CARDIOVASCULAR DEATH, NON-FATAL MYOCARDIAL INFARCTION OR NON-FATAL STROKE) IN ADULTS WITH TYPE 2 DIABETES MELLITUS AND ESTABLISHED CARDIOVASCULAR DISEASE
4MG/3ML (1.34MG/ML)	OZEMPIC	NOVO	N209637	April 9, 2019	RX	SOLUTION	SUBCUTANEOUS	Jan. 16, 2023	REDUCE THE RISK OF MAJOR ADVERSE CARDIOVASCULAR EVENTS (CARDIOVASCULAR DEATH, NON-FATAL MYOCARDIAL INFARCTION OR NON-FATAL STROKE) IN ADULTS WITH TYPE 2 DIABETES MELLITUS AND ESTABLISHED CARDIOVASCULAR DISEASE
14MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	Jan. 16, 2023	ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME
3MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	Jan. 16, 2023	ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME
7MG	RYBELSUS	NOVO	N213051	Sept. 20, 2019	RX	TABLET	ORAL	Jan. 16, 2023	ADDITION OF INFORMATION TO CLINICAL STUDIES SECTION REGARDING CARDIOVASCULAR OUTCOME

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Glucagon-like peptide 1 receptor	GPCR	P43220	GLP1R_HUMAN	AGONIST	IC50	9.42		SCIENTIFIC LITERATURE	DRUG LABEL

External reference:

ID	Source
53AXN4NNHX	UNII
9113	INN_ID
D10025	KEGG_DRUG
DB13928	DRUGBANK_ID
CHEMBL2108724	ChEMBL_ID
56843331	PUBCHEM_CID
9724	IUPHAR_LIGAND_ID
C000591245	MESH_SUPPLEMENTAL_RECORD_UI
764284009	SNOMEDCT_US
764283003	SNOMEDCT_US
1991302	RXNORM
017424	NDDF
33346	MMSL
d08688	MMSL
4037164	VANDF

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Ozempic	HUMAN PRESCRIPTION DRUG LABEL	1	0169-4132	INJECTION, SOLUTION	1.34 mg	SUBCUTANEOUS	NDA	20 sections
Ozempic	HUMAN PRESCRIPTION DRUG LABEL	1	0169-4136	INJECTION, SOLUTION	1.34 mg	SUBCUTANEOUS	NDA	20 sections
RYBELSUS	HUMAN PRESCRIPTION DRUG LABEL	1	0169-4303	TABLET	3 mg	ORAL	NDA	18 sections
RYBELSUS	HUMAN PRESCRIPTION DRUG LABEL	1	0169-4307	TABLET	7 mg	ORAL	NDA	18 sections
RYBELSUS	HUMAN PRESCRIPTION DRUG LABEL	1	0169-4314	TABLET	14 mg	ORAL	NDA	18 sections
Ozempic	HUMAN PRESCRIPTION DRUG LABEL	1	70518-2143	INJECTION, SOLUTION	1.34 mg	SUBCUTANEOUS	NDA	19 sections