Saxagliptin

Structural formula
General
Non-proprietary name	Saxagliptin
Molecular formula	C 18 H 25 N 3 O 2
External identifiers / databases
PubChem	11243969
ChemSpider	9419005
DrugBank	DB06335
Wikidata	Q3121121
Drug information
ATC code	A10 BH03
Drug class	Antidiabetic drugs , inhibitors of dipeptidyl peptidase 4
Mechanism of action	Competitive inhibition of dipeptidyl peptidase 4
properties
Molar mass	315.41 g mol −1
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 302-315-319-335
	P: 261-280-305 + 351 + 338
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Saxagliptin is an orally active drug for the treatment of diabetes mellitus type 2. It belongs to the group of active substances of the inhibitors of dipeptidyl peptidase 4 (also called gliptins ), which are based on the effect of glucagon-like peptide 1 (GLP-1) in addition to incretin mimetics . Saxagliptin was developed by Bristol-Myers Squibb and AstraZeneca .

synthesis

Bristol-Myers Squibb's synthesis route for saxagliptin begins with an amidation of N -Boc-3-hydroxyadamantylglycine ( 2 ) with methanoprolinamide ( 3 ) and EDC as the coupling reagent. The amide is then dehydrated with trifluoroacetic anhydride and the cleavage of the Boc protective group then gives saxagliptin.

Mechanism of action

The effect of saxagliptin is based - like that of the other gliptins - on the inhibition of the enzyme dipeptidyl peptidase 4 , which is responsible for the breakdown of the hormone glucagon-like peptide 1 (GLP-1). Since the GLP-1 formed by the L cells of the intestinal mucosa stimulates the release of the blood sugar lowering hormone insulin and reduces the secretion of the insulin counterpart glucagon , an inhibition of dipeptidyl peptidase 4 by saxagliptin leads to a lowering of the blood sugar level in diabetic patients. The effect of GLP-1 in the context of the insulin response is known as the incretin effect .

Therapeutic use

Saxagliptin is indicated as monotherapy for diabetes mellitus when diet and exercise are insufficient and metformin is not suitable. Saxagliptin is used to treat non-insulin-dependent type 2 diabetes mellitus and is usually taken once a day in adults in a single dose of 2.5 to 5 milligrams. It is not primarily used for the short-term treatment of hyperglycaemia or for targeted use before meals, but rather to improve the body's own insulin response during long-term treatment. In this indication, saxagliptin was approved in the EU as the third active ingredient from the group of gliptins after sitagliptin and vildagliptin in October 2009 under the name Onglyza . A combination product with metformin has also been approved since 2011 ( Komboglyze ).

Saxagliptin can be considered as an alternative to insulin therapy in type 2 diabetes when other oral antidiabetic agents fail in monotherapy or combination therapy.

Side effects, contraindications and interactions

The most commonly reported side effects are upper respiratory tract infections, urinary tract infections and headache.

Trade names

Monopreparations

Onglyza (EU, CH)

Combination preparations

with metformin : Komboglyze (EU), Duoglyze (CH), Kombiglyze (CH, USA)
with dapagliflozin : Qtern (EU)

Web links

European public assessment report (EPAR) and Product of the European Medicines Agency (EMA) for Onglyza
European Public Assessment Report (EPAR) and European Medicines Agency (EMA) product information for Komboglyze
European Public Assessment Report (EPAR) and European Medicines Agency (EMA) product information for Qtern
G-BA benefit assessment procedure for the active ingredient saxagliptin
G-BA benefit assessment procedure for the active ingredient saxagliptin / metformin

literature

DJ Drucker & MA Nauck (2006): The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes. In: Lancet. Vol. 368, pp. 1696-1705. PMID 17098089 , doi : 10.1016 / S0140-6736 (06) 69705-5 .

Individual evidence

↑ ^a ^b AChemBlock: Saxagliptin 98% - CAS 361442-04-8 , accessed December 21, 2019
^ Scott A. Savage, Gregory S. Jones, Sergei Kolotuchin, Shelly Ann Ramrattan, Truc Vu, Robert E. Waltermire: Preparation of Saxagliptin, a Novel DPP-IV Inhibitor . In: Org. Process Res. Dev. Band 13 , no. 6 , 2009, p. 1169–1176 , doi : 10.1021 / op900226j .
↑ Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , p. 158.
↑ Jeffrey K. Aronson: Side Effects of Drugs Annual A worldwide yearly survey of new data in adverse drug reactions . Newnes, 2014, ISBN 0-444-62636-0 , pp. 769 ( limited preview in Google Book search).

[achemblock.com-1] AChemBlock: Saxagliptin 98% - CAS 361442-04-8 , accessed December 21, 2019

[2] Scott A. Savage, Gregory S. Jones, Sergei Kolotuchin, Shelly Ann Ramrattan, Truc Vu, Robert E. Waltermire: Preparation of Saxagliptin, a Novel DPP-IV Inhibitor . In: Org. Process Res. Dev. Band 13 , no. 6 , 2009, p. 1169–1176 , doi : 10.1021 / op900226j .

[3] Richard Daikeler, idols Use, Sylke Waibel: diabetes. Evidence-based diagnosis and therapy. 10th edition. Kitteltaschenbuch, Sinsheim 2015, ISBN 978-3-00-050903-2 , p. 158.

[Jeffrey_K._Aronson-4] Jeffrey K. Aronson: Side Effects of Drugs Annual A worldwide yearly survey of new data in adverse drug reactions . Newnes, 2014, ISBN 0-444-62636-0 , pp. 769 ( limited preview in Google Book search).