Dapagliflozin

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Dapagliflozin
Dapagliflozin structure.svg
Systematic (IUPAC) name
(2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
Clinical data
Trade namesForxiga, Farxiga
AHFS/Drugs.comUK Drug Information
Licence dataEMA:Link, US FDA:link
Pregnancy cat.
Legal status
RoutesOral
Identifiers
CAS number461432-26-8 N
ATC codeA10BX09
PubChemCID 9887712
ChemSpider8063384 YesY
UNII1ULL0QJ8UC YesY
ChEMBLCHEMBL429910 YesY
SynonymsBMS-512148
Chemical data
FormulaC21H25ClO6 
Mol. mass408.873 g/mol
 N (what is this?)  (verify)
 
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Dapagliflozin
Dapagliflozin structure.svg
Systematic (IUPAC) name
(2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
Clinical data
Trade namesForxiga, Farxiga
AHFS/Drugs.comUK Drug Information
Licence dataEMA:Link, US FDA:link
Pregnancy cat.
Legal status
RoutesOral
Identifiers
CAS number461432-26-8 N
ATC codeA10BX09
PubChemCID 9887712
ChemSpider8063384 YesY
UNII1ULL0QJ8UC YesY
ChEMBLCHEMBL429910 YesY
SynonymsBMS-512148
Chemical data
FormulaC21H25ClO6 
Mol. mass408.873 g/mol
 N (what is this?)  (verify)

Dapagliflozin (INN/USAN,[1] trade name Farxiga in the US and Forxiga in the EU) is a drug used to treat type 2 diabetes. It was developed by Bristol-Myers Squibb in partnership with AstraZeneca. Although dapagliflozin's method of action would operate on both types of diabetes[1] and other conditions resulting in hyperglycemia, clinical trials are just now starting to include patients with type 1 diabetes.[2][3]

In July 2011 a US Food and Drug Administration (FDA) committee recommended against approval until more data were available.[4] The FDA approved dapagliflozin on January 8, 2014 for glycemic control, along with diet and exercise, in adults with type 2 diabetes.[5]

In April 2012, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency issued a positive opinion on the drug. It is now marketed in a number of European countries including the UK and Germany.

Mechanism of action[edit]

Dapagliflozin inhibits subtype 2 of the sodium-glucose transport proteins (SGLT2), which is responsible for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter causes blood glucose to be eliminated through the urine.[6] The efficacy of this medication class has yet to be determined, but in initial clinical trials, dapagliflozin lowers HbA1c by 0.90 percentage points when added to metformin.[7]

Side effects[edit]

Since dapagliflozin leads to heavy glycosuria (sometimes up to about 70 grams per day) it can lead to rapid weight loss and tiredness. The glucose acts as an osmotic diuretic (this effect is the cause of polyuria in diabetes) which can lead to dehydration. The increased amount of glucose in the urine can also worsen the infections already associated with diabetes, particularly urinary tract infections and thrush (candidiasis). Dapagliflozin is also associated with hypotensive reactions.

Selectivity[edit]

The IC50 for SGLT2 is less than one thousandth of the IC50 for SGLT1 (1.1 versus 1390 nmol/l), so that the drug does not interfere with intestinal glucose absorption.[8]

References[edit]