FDA Advised Not to Approve Dapagliflozin for Diabetes

Yesterday a panel voted 9-6 advising the FDA not to approve dapagliflozin, a diabetes drug that forces the body to dump sugar. The panel cited possible liver damage and signals of breast and bladder cancer as a reason for their decision.

With the vote being 9-6, it is unclear whether the FDA will approve the drug or not. They will however, be asking Bristol-Myers Squibb and AstraZeneca—both companies manufacture the drug—to gather more data on the side effects of the drug. The FDA’s request for more data could come before or after its approval of dapagliflozin.

The new drug works by allowing sugar to pass out of the body through the urine, thus lowering the blood sugar without affecting insulin levels in diabetic patients. Usually the kidneys recycle sugar back into the body, but dapagliflozin inhibits the transporter molecule, SGLT-2.

Another result of the new diabetes drug is weight loss. Clinical trials showed that, in type 2 diabetes patients, those who took dapagliflozin for at least 6 months lost anywhere from 1 to 5 pounds. Thirty percent of diabetic patients who took the drug plus metformin lost 5% of their original body weight.

One of the panels’ main reasons for not advising the FDA to approve this drug is that in diabetic patients kidney function is often lowered. Any loss of function of the kidneys makes dapagliflozin much less effective. Thus the patient’s kidney function will need to be tested prior to being given this new drug and it will only be given to patients with significant kidney function.

One of the noted side effects of dapagliflozin is that because sugar is forced out through the urine, the patient is at an increased risk for urinary tract and general infections. Other side effects include dehydration and heat intolerance.

Clinical trials of dapagliflozin observed 4300 patients with type 2 diabetes, who received the drug for over a year and 441 patients who were treated for at least 2 years.

After the trials concluded, 5 patients showed signs of liver toxicity, one of which classified the liver toxicity as “probable diagnosis of mild to moderately severe dapagliflozin-induced liver injury.”

Another troublesome result showed that 9 patients who took dapagliflozin developed bladder cancer. Another 9 patients taking the drug developed breast cancer. There was 1 case of bladder cancer in a patient not taking dapagliflozin and no breast cancer developments in those not taking the drug.