Products
Dapagliflozin is commercially available in the form of film-coated tablets (Forxiga). It was approved in the EU in 2012 and in the United States and many countries in 2014. Dapagliflozin is also combined fixed with metformin (Xigduo XR). A fixed combination with saxagliptin was approved in 2017 (Qternmet film-coated tablets). Qternmet XR is a combination with dapagliflozin and with metformin. Qtrilmet combines metformin, saxagliptin, and dapagliflozin.
Structure and properties
Dapagliflozin (C21H25ClO6, Mr = 408.9 g/mol) is a C-glucoside that is stable to glucosidases in the intestine. It has certain structural similarities to phlorizin, a nonspecific SGLT inhibitor derived from apple tree bark and a precursor of the modern agents. In the drug, it is present as dapagliflozin-((2S)-propane-1,2-diol) (1:1) 1 – H2O.
Effects
Dapagliflozin (ATC A10BX09) has antidiabetic and antihyperglycemic properties and may reduce body weight. It is a competitive, reversible, potent, and selective inhibitor of sodium–glucose co-transporter 2 (SGLT2). This transporter is responsible for the reabsorption of glucose at the proximal tubule of the nephron. Inhibition leads to increased excretion of the sugar via the urine. The mechanism of action is independent of insulin, unlike other antidiabetic agents. SGLT1, which is also found in the intestine, is not inhibited by dapagliflozin.
Indications
For the treatment of type 2 diabetes mellitus.
Dosage
According to the SmPC. Due to the long half-life of 16-17 hours, once-daily administration is sufficient. The tablets can be taken independently of meals.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Adverse effects
The most common possible adverse effects include urinary tract infections, genital tract infections, disturbances in lipid metabolism, increased urine output, and urinary discomfort. These side effects are largely due to the increased glucose concentration in the urine. Hypoglycemia is rarely observed with monotherapy but may occur in combination with sulfonylureas and insulins. The safety of the agent has been questioned. In clinical trials, slightly more cases of bladder and breast cancer were observed in the dapagliflozin group. However, whether there is actually an association is controversial.