Twenty-six million Americans have diabetes and 79 million have prediabetes. A new class of drugs called SGLT2 inhibitors works in a totally new way.
Instead of affecting the supply or use of insulin, as most current drugs do, the new drugs lower blood sugar by causing sugar to be excreted in urine. The resulting loss of calories helps diabetics, who tend to be overweight, lose weight.
A potential advantage of these drugs is that their mechanism of action is independent of insulin, making it potentially easy to combine SGLT2 inhibitors with other drugs. Many other diabetes drugs work either by providing the body with insulin, inducing the pancreas to secrete more insulin or making the body more sensitive to insulin.
Moreover, because so many calories are now flowing out in the urine, the SGLT2 inhibitors help people lose a little weight. That could be of some benefit because many people with diabetes are overweight and because some other diabetes drugs can cause weight gain.
In clinical trials, patients receiving dapagliflozin lost an average of about five pounds more than those getting a placebo after six months. They also experienced a slight reduction in blood pressure.
One drawback, however, is that the extra sugar in the urine makes the urinary tract and genitals more hospitable to micro-organisms, leading to an increase in infections. What seemed to concern the F.D.A. reviewers more than these infections was a possible increased risk of breast and bladder cancers.
Nine women, or 0.4 percent of those who took the drug, got breast cancer compared with one woman, or 0.09 percent, of those in the control group, according to AstraZeneca and Bristol-Myers. For bladder cancer, the rate was nine cases, or 0.3 percent, for those taking the drug compared with one case, or 0.05 percent, for those in the control group.
The companies argue that when all types of cancer, not just breast and bladder cancer, are considered, there is no increased risk for those taking dapagliflozin. They also say that some of the cancers were diagnosed so soon after the start of the trial that they were unlikely to be linked to the drug.
Although dapagliflozin has been rejected in the U.S. to this point, in April 2012 advisers to the European drug regulator recommended approval. While acknowledging safety concerns including a potential cancer risk, the European Medicines Agency’s Committee for Medicinal Products for Human Use, or CHMP, said that it recommended marketing authorization for dapagliflozin, which the companies plan to market under the brand Forxiga for treatment of type 2 diabetes. It is now up to the European Commission to decide on final approval, which could come within months.