BMS/AZ resubmits SGLT-2 inhibitor Dapagliflozin to FDA
By Kelly Close
On July 25, Bristol-Myers Squibb (BMS) and AstraZeneca (AZ) announced the resubmission of Forxiga (dapagliflozin), their SGLT-2 inhibitor for type 2 diabetes, to the FDA. Forxiga is currently approved in Europe, Australia, Brazil, Mexico, and New Zealand. The companies were asked by the FDA in January 2012 to provide additional data before approval would be considered in the US. The resubmission means FDA must now decide whether to approve the new drug by January 14, 2014.
The new SGLT-2 inhibitor class of type 2 drugs works by causing users to excrete excess glucose through their urine. There are currently only two SGLT-2 inhibitors on the market for type 2 patients: J&J Janssen’s Invokana (canagliflozin) in the US, and BMS/AZ’s Forxiga in Europe. For more information on SGLT-2 inhibitors and how they work, see learning curve in diaTribe #51.
In trials, people using dapagliflozin typically reduced their A1c by 0.8-1% over a year from a baseline of around 8.0%. Patients also had some weight loss and reductions in blood pressure. While there was originally concern about increased rates of bladder and breast cancer, there haven’t been any major pieces written yet by researchers on this front. Increased urinary tract and genital infections (see new now next in diaTribe #35) were also viewed as a risk, though manageable.
SGLT-2 inhibitors have also shown promise in type 1 diabetes. Last month at ADA, researchers shared results from a 14-day trial of dapagliflozin in type 1 patients. Trial participants saw a 10-20 mg/dl drop in their average daily blood glucose (the trial was too short to measure A1c), used 16-19% less total insulin, and experienced less glycemic variability (see conference pearls in diaTribe #56). Hypoglycemia appeared slightly higher in the group on dapagliflozin, though it’s still too early to quantify exactly how much higher, since four doses of dapagliflozin were tested. Lexicon and Boehringer Ingelheim/Lilly have also presented promising studies of their SGLT-2 inhibitors in type 1 diabetes. Looking to the future, we are especially interested in seeing SGLT-2 inhibitors combined with other glucose lowering medications in a single pill – these are known as fixed dose combinations. It could be that in a decade, the notion of a single formulation pill may be only a memory. –NL/KC
