Dapagliflozin
Encyclopedia
Dapagliflozin is an experimental drug being studied by Bristol-Myers Squibb
in partnership with AstraZeneca
as a potential treatment for type 1 and 2 diabetes. Although dapagliflozin's method of action would operate on either type of diabetes or other conditions resulting in hyperglycemia
, the current clinical trials specifically exclude participants with Type 1 diabetes.
In July 2011 an FDA committee recommended against approval until more data was available. The Prescription Drug User Fee Act
(PDUFA) date for dapagliflozin for the treatment of Type 2 diabetes was extended three months by the FDA to January 28, 2012.
(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.
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 the intestinal glucose absorption.
Bristol-Myers Squibb
Bristol-Myers Squibb , often referred to as BMS, is a pharmaceutical company, headquartered in New York City. The company was formed in 1989, following the merger of its predecessors Bristol-Myers and the Squibb Corporation...
in partnership with AstraZeneca
AstraZeneca
AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...
as a potential treatment for type 1 and 2 diabetes. Although dapagliflozin's method of action would operate on either type of diabetes or other conditions resulting in hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
, the current clinical trials specifically exclude participants with Type 1 diabetes.
In July 2011 an FDA committee recommended against approval until more data was available. The Prescription Drug User Fee Act
Prescription Drug User Fee Act
The Prescription Drug User Fee Act was a law passed by the United States Congress in 1992 which allowed the Food and Drug Administration to collect fees from drug manufacturers to fund the new drug approval process...
(PDUFA) date for dapagliflozin for the treatment of Type 2 diabetes was extended three months by the FDA to January 28, 2012.
Method of action
Dapagliflozin inhibits subtype 2 of the sodium-glucose transport proteinsSodium-glucose transport proteins
Sodium-dependent glucose cotransporters are a family of glucose transporter found in the intestinal mucosa of the small intestine and the proximal tubule of the nephron . They contribute to renal glucose reabsorption...
(SGLT2), which is responsible for at least 90% of the glucose reabsorption
Reabsorption
In physiology, reabsorption or tubular reabsorption is the flow of glomerular filtrate from the proximal tubule of the nephron into the peritubular capillaries, or from the urine into the blood...
in the kidney. Blocking this transporter causes blood glucose to be eliminated through the urine.
Selectivity
The IC50IC50
The half maximal inhibitory concentration is a measure of the effectiveness of a compound in inhibiting biological or biochemical function. This quantitative measure indicates how much of a particular drug or other substance is needed to inhibit a given biological process by half...
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 the intestinal glucose absorption.