What is dapagliflozin?
Dapagliflozin is an oral antidiabetic applique for the treatment of type 2 diabetes. Dapagliflozin was developed by the US pharmaceutical company Bristol-Myers Squibb in partnership with the British pharmaceutical company AstraZeneca.
Pharmacology
Mechanism of Action
Dapagliflozin is a selective SGLT-2 inhibitors (sodium dependent glucose transporter). SGLT2 is a protein that is reabsorbed in the proximal tubule of the kidney sodium and glucose from the primary and thus responsible for the majority of the glucose absorption of the kidney. The inhibition of SGLT2 in existing hyperglycemia causes increased excretion of glucose in the urine and this glucosuria support to a small extent a weight loss. Unlike his predecessors in the group of SGLT-2 inhibitors, the O-glycosides, dapagliflozin is stable against β-glycosidases and therefore has a longer plasma half-life.
Approval status
Dapagliflozin 2012 was approved by the European Medicines Agency (EMA) under the trade name Forxiga ™. 2014, the combination preparation of dapagliflozin and metformin was approved under the trade name Xigduo ™.
In the US, the Food and Drug Administration (FDA) in 2012 had initially denied approval for dapagliflozin because of safety concerns. Further studies should clarify whether the drug bladder cancer, breast cancer or liver damage may cause. In January 2014, was admitted by the FDA for the US market, since the new data from studies and applications allowed an appropriate assessment. Where the preparation is sold under the trade name Farxiga.
Dapagliflozin is in the EU for use in adults with type 2 diabetes patients admitted according to the current prescribing information for monotherapy when diet and exercise alone the blood sugar is not adequately control in patients for whom use of metformin is due to an incompatibility is considered inappropriate or in combination with other blood sugar-lowering drugs, including insulin, if they do not control blood sugar sufficiently with diet and exercise.
According to the current Code of Reimbursement in Austria is a refund according to the rules possible in patients with diabetes type 2 Quote:. "The treatment must be started from an HbA1c greater than 7 Treatment with dapagliflozin has only as second-line therapy as monotherapy in metformin. intolerant or -Kontraindikation if with less expensive therapeutic alternatives from the open area (ATC code A10BB, A10BF, A10BX) demonstrated the Auslangen can not be found, or as a combination therapy with metformin or as a combination therapy with sulfonylureas or as combination therapy with insulin with or without metformin to take place. dapagliflozin will not be refunded in combination with pioglitazone, glinides or DPP-IV inhibitors. No use in patients over 75 years, with neoplasms of the urinary bladder or in moderate and severe renal impairment defined by creatinine clearance less than 60 ml / min. Regular monitoring of renal values according to the SPC. Every 6 months is to perform a HbA1c determination. Dapagliflozin is suitable for a chef (control) medical long-term permit for 6 months (L6). "
Review / Early Evaluation
In Germany Forxiga since November 2012 according to the authorization in use. After a temporary withdrawal from the German market in December 2013, the drug was launched in February 2014 after an agreement on the price with the Statutory Health Insurance Funds Association again in the sales.
As part of the early benefit assessment (see also AMNOG) had set a sulphonylurea (glibenclamide or glimepiride) as appropriate comparator therapy, the Federal Joint Committee. Since the manufacturer had to provide comparative data, the Institute for Quality and Efficiency in Health Care (IQWiG) had recognized an additional benefit of dapagliflozin to be unoccupied. The G-BA had confirmed the assessment IQWiG and decided the corresponding change in drug policy in June 2013. This decision of the G-BA was supported by the German Diabetes Association (DDG) heavily criticized the turn recognizes the clear added value of Forxiga for patients with type 2 diabetes. As part of the Evaluation of the combination of dapagliflozin / metformin (trade name Xigduo®) IQWiG criticized "added value of fixed-dose combination of dapagliflozin and metformin is not used".
In previous studies occurred in patients treated with dapagliflozin compared to placebo significantly more frequent genital and less frequent urinary tract infections. There was a non-significant increase in the number of malignant bladder and breast tumors in the studies. The cause of these diseases is the subject of intensive follow-up observations in phase IV.