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Dapagliflozin

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Dapagliflozin
Clinical data
Trade namesForxiga, Farxiga
Other namesBMS-512148
AHFS/Drugs.comUK Drug Information
License data
Routes of
administration		Oral
ATC code
Legal status
Legal status
Identifiers
  • (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.167.331 Edit this at Wikidata
Chemical and physical data
FormulaC21H25ClO6
Molar mass408.873 g/mol g·mol−1
3D model (JSmol)
  • Clc1ccc(cc1Cc2ccc(OCC)cc2)[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O
  • InChI=1S/C21H25ClO6/c1-2-27-15-6-3-12(4-7-15)9-14-10-13(5-8-16(14)22)21-20(26)19(25)18(24)17(11-23)28-21/h3-8,10,17-21,23-26H,2,9,11H2,1H3/t17-,18-,19+,20-,21+/m1/s1 checkY
  • Key:JVHXJTBJCFBINQ-ADAARDCZSA-N checkY
 ☒NcheckY (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

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

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

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

  1. ^ a b Statement on a nonproprietory name adopted by the USAN council
  2. ^ Efficacy and Safety of Dapagliflozin, Added to Therapy of Patients With Type 2 Diabetes With Inadequate Glycemic Control on Insulin, ClinicalTrials.gov, April 2009
  3. ^ Trial Details for Trial MB102-020, Bristol-Myers Squibb, May 2009
  4. ^ "FDA panel advises against approval of dapagliflozin". 19 July 2011.
  5. ^ "FDA approves Farxiga to treat type 2 diabetes". 8 January 2014.
  6. ^ Prous Science: Molecule of the Month November 2007
  7. ^ UEndocrine: Internet Endocrinology Community
  8. ^ Schubert-Zsilavecz, M, Wurglics, M, Neue Arzneimittel 2008/2009
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