Dapagliflozin

Dapagliflozin, sold under the brand name Farxiga among others, is a medication used to treat type 2
diabetes. It is of the gliflozin class. It was developed by Bristol-Myers Squibb in partnership with
AstraZeneca.

Medical uses

Dapagliflozin used to improve glycemic control, along with diet and exercise, in adults with type 2
diabetes.[2] SGLT2 inhibitors, including dapagliflozin, reduce the likelihood of hospitalization for
congestive heart failure or progression of renal disease in persons with diabetes mellitus type 2 and
reduce the likelihood of stroke and heart attack in persons with diabetes mellitus type 2 who have
known atherosclerotic vascular disease.[3]

In 2012, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines
Agency issued a positive opinion on the drug.[4] It is now marketed in a number of European
countries.[5]

Adverse 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). Rarely, use of a SGLT2 drug, including dapagliflozin, is associated with necrotizing
fasciitis of the perineum, also called Fournier gangrene.[6]

Dapagliflozin is also associated with hypotensive reactions. There are concerns it may increase the risk
of diabetic ketoacidosis.[7]

Mechanism of action

Dapagliflozin inhibits subtype 2 of the sodium-glucose transport proteins (SGLT2) which are responsible
for at least 90% of the glucose reabsorption in the kidney. Blocking this transporter mechanism causes
blood glucose to be eliminated through the urine.[8] In clinical trials, dapagliflozin lowered HbA1c by 0.6
versus placebo percentage points when added to metformin.[9]

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.[10]